TY - JOUR. T1 - Neural crest cell differentiation and carcinogenesis. T2 - Capability of goldfish erythrophoroma cells for multiple differentiation and clonal polymorphism in their melanogenic variants. AU - Matsumoto, Jiro. AU - Wada, Kumiko. AU - Akiyama, Toyoko. PY - 1989/5. Y1 - 1989/5. N2 - Multiple differentiation shown by a single cell line (GEM 81) of goldfish erythrophoroma (tumors of integumental erythrophores) cells after administration of chemical induction in vitro includes 1) melanogenesis, 2) formation of reflecting platelets, 3) synthesis of pteridines heterogeneous to this species, 4) formation of dermal skeletons such as teeth and fin rays, 5) production of neuronal characters, and 6) genesis of lentoid bodies. Melanogenic cells, highest in inducibility, also show remarkable phenotypic diversification in their cell morphology, pigmentation, and physiologic response. In this paper, the following findings are presented; a) multiple differentiation shown by erythrophoroma cells ...

TY - JOUR. T1 - Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen. AU - Kikuchi, Kentaro. AU - Lian, Zhe Xiong. AU - He, Xiaosong. AU - Ansari, Aftab A.. AU - Ishibashi, Miyuki. AU - Miyakawa, Hiroshi. AU - Shultz, Leonard D.. AU - Ikehara, Susumu. AU - Gershwin, M. Eric. PY - 2003/6. Y1 - 2003/6. N2 - Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC) directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naïve B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plasma cells in spleen increased by 100 fold after transplantation. Plasma cell numbers correlated with the detection of human IgM and IgG in serum, indicating ...

Movahednia, Mohammad Mehdi Ehdi, Kidwai, Fahad Karim Arim, Zou, Yu, Tong, Huei Jinn, Liu, Xiaochen, Islam, Intekhab, Toh, Wei Seong, Raghunath, Michael, Cao, Tong (2015). Differential effects of the extracellular microenvironment on human embryonic stem cell differentiation into keratinocytes and their subsequent replicative life span. Tissue Engineering - Part A 21 (42223) : 1432-1443. ScholarBank@NUS Repository. https://doi.org/10.1089/ten.tea. ...

TY - JOUR. T1 - Effects on cell differentiation and cell survival rate of the photocurable resins for stereolithography. AU - Imai, Koichi. AU - Akiyama, Mari. AU - Tamura, Isao. AU - Morita, Shosuke. AU - Iseki, Tomio. AU - Yoshida, Hiroaki. AU - Matsumoto, Kazuhiro. AU - Shida, Muneyasu. AU - Ogawa, Fumiya. AU - Sawai, Hirofumi. AU - Ohkubo, Tadashi. AU - Hoshika, Tomohiro. AU - Nishitani, Yoshihiro. PY - 2015. Y1 - 2015. N2 - Stereolithography, a new molding technique for polymeric materials, should also be applied as a novel method to mold biomaterials into complex curved surfaces in a short period of time using three-dimensional CAD data, which cannot be achieved with conventional cutting methods. However, photocurable resins with potent toxicity have not traditionally been applied directly in vivo as medical materials. For their application to dental molding, photocurable resins with fewer biological risks should be developed. In the present study, we compared the differentiation rates of ...

The objective of this paper is to provide the fundamental mathematical formula to predict the effect of magnetic fields (MF) on stem cell differentiation. The data were reviewed from journals related to the effects of magnetic fields on stem cell differentiation. These data were given a value for differentiation which is related to their MF strength with these conditions; MF strength that does not affect the stem cell differentiation given the value of zero, MF strength that results in stem cells death given the value of 1, and the MF strength that affects stem cells The differentiation given the value between 0.1 and 0.9. graph was plotted according to these data and the mathematical equation is designed from the graph. From this review, we suggest that the intensity of MF that can affect the stem cell differentiation is between 600μT and 9.4T in which the cell differentiation will not occur with intensity of less than 10μT and intensity of more than 12T will cause the death of stem cells. We ...

Title:Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells. VOLUME: 16 ISSUE: 9. Author(s):Pier M. Biava, Silvia Canaider, Federica Facchin, Eva Bianconi, Liza Ljungberg, Domenico Rotilio, Fabio Burigana and Carlo Ventura. Affiliation:Scientific Institute of Research and Care Multimedica, Milano, Italy.. Keywords:Stem cell differentiation stage factors, cancer stem cells, human adipose-derived stem cells, cell reprogramming, cancer therapies, psoriasis, anti-aging treatments, neurodegeneration.. Abstract:In spite of the growing body of evidence on the biology of the Zebrafish embryo and stem cells, including the use of Stem Cell Differentiation Stage Factors (SCDSFs) taken from Zebrafish embryo to impact cancer cell dynamics, comparatively little is known about the possibility to use these factors to modulate the homeostasis of normal human stem cells or to modulate the behavior of cells involved in ...

TY - JOUR. T1 - Proliferation and differentiation characteristics of neural stem cells during course of cerebral cortical histogenesis. AU - Mitsuhashi, Takayuki. AU - Takahashi, Takao. PY - 2016/1/1. Y1 - 2016/1/1. N2 - Recent advancements in the research field of stem cell biology have enabled the realization of regenerative medicine in various systems of the body, including the central nervous system. However, fundamental knowledge regarding how neural stem cells divide and generate young neurons in mammals, especially in vivo, is still inadequate. In this article, we shall summarize the concept of cell cycle/division of neural stem cells that generate projection neurons in the murine cerebral cortex. We shall also review the molecular mechanisms that modulate the critical parameters related to the cell cycle regulatory mechanisms, with special reference to the cell cycle regulatory protein p27Kip1, an inhibitor of progression of the cell cycle at the G1 phase. A better understanding of the ...

In the epidermis, one of the earliest characterized events in keratinocyte differentiation is the coordinate induction of a pair of keratins specifically expressed in suprabasal cells, keratin 1 (K1) and keratin 10 (K10). Both in vivo and in vitro, extracellular calcium is necessary for several biochemical and structural changes during keratinocyte differentiation. However, it has been unclear if calcium serves as a differentiation signal in keratinocytes. In these studies, expression of suprabasal keratin mRNA and protein is used to test whether the initial differentiation of primary mouse keratinocytes in vitro is dependent on changes in the concentration of extracellular calcium. K1 mRNA was expressed at low levels in cultures of keratinocytes growing on plastic in 0.05 mM calcium but in attached cells was not further induced by increases in the concentration of extracellular calcium. Suspension of the keratinocytes into semi-solid medium induced a rapid and substantial increase in both ...

This protocol describes highly efficient means of deriving functional human hepatocyte-like cells from hESCs. The significance of this in vitro technology is the ability to generate homogeneous and limitless cultures of high fidelity human hepatocyte-like cells for applied biology. In this protocol, no functional assays such as detoxification, synthesis of clotting factors, metabolism of ammonia or excretion of bilirubin, have been shown.. ...

The majority of studies on stem cell differentiation have so far been based in vivo, on live animal models. The usefulness of such models is limited, since it is much more technically challenging to conduct molecular studies and genetic manipulation on live animal models compared to in vitro cell culture. Hence, it is imperative that efficient protocols for directing stem cell differentiation into well-defined lineages in vitro are developed. The development of such protocols would also be useful for clinical therapy, since it is likely that the transplantation of differentiated stem cells would result in higher engraftment efficiency and enhanced clinical efficacy, compared to the transplantation of undifferentiated stem cells. The in vitro differentiation of stem cells, prior to transplantation in vivo, would also avoid spontaneous differentiation into undesired lineages at the transplantation site, as well as reduce the risk of teratoma formation, in the case of embryonic stem cells. Hence, ...

Embryonic stem cells (ES cells) represent a population of self renewing pluripotent cells, capable of differentiating into derivatives of the 3 embryonic germ layers and are therefore a promising source material for generation of replacement pancreatic beta cells for transplantation in type 1 diabetes. ES cells can be induced to undergo unregulated differentiation when cultured as floating clusters (embryoid bodies). Successful generation of pancreatic endocrine cells from ES cells has thus far relied on embryoid body formation as an initial step. However, selection and expansion of sufficient quantities of insulin -secreting cells has remained a problem. Data presented here show a novel route for ES cell differentiation avoiding embryoid body formation and resulting in a cell population that expresses markers of pancreatic endocrine cell differentiation. The CCE mouse ES cell line was cultured in standard ES cell medium. Cultures were grown to high confluence to create large differentiated ...

This protocol describes for the first time, a detailed method to generate vascular smooth muscle cells (SMC) from its three developmental contributers: neuroectoderm, paraxial mesoderm and lateral plate mesoderm progenitor cells, all of which can be derived from human embryonic stem cells. The derived SMCs display contractile ability upon stimulation and have been shown to support vessel formation when transplanted in-vivo. The developmental origin-specific SMC subtypes, enable the study of unique features of the derived SMC subtypes, such as extracellular matrix degradation ...

Oct4 is one of the master pluripotency genes that controls differentiation of human embryonic stem cells (hESCs). We generated HES2 and HES3 hESC lines stably transduced with lentivirus carrying Oct4 short hairpin RNA (shRNA) that display 80-90% reduction of Oct4 expression. Analysis of pluripotency marker expression shows that these Oct4 shRNA-transduced hESCs display normal wild-type expression levels of the pluripotency marker CD9 but an absence of GCTM2 expression. These hESC-derived adipocyte precursor cells display a characteristic morphology and can be propagated and cryopreserved as a standard stem cell line. Interestingly, Oct4 shRNA-transduced hESCs display a remarkably high lineage-specific spontaneous differentiation toward adipocytes. After two weeks of spontaneous differentiation under feeder-free conditions, 60-70% of cells display a mature adipocyte morphology as well as the expression of multiple adipocyte-specific mRNAs as assessed by RT-PCR. The upregulation of trophoblast, ...

Thesis 1990 , In Vitro Differentiation Induction Of Human Normal And Leukaemic Myeloid Progenitor Cells, In Vitro Differentiation Induction Of Human Normal And Leukaemic Myeloid Progenitor Cells =

Diverse types of stem cells represent a potentially attractive source of cardiac cells for the treatment of cardiovascular diseases. However, most of the functional benefits reported for stem cell have been modest and mainly due to paracrine effects rather than differentiation into cardiomyocytes of the applied cells. Therefore, new tools need to be developed in order to improve the efficiency of stem cell differentiation towards specific cardiovascular lineages. Here we show that microRNAs that display early differential expression during ventricular maturation, such as miR-27b, inhibits cardiac differentiation from mouse embryonic stem cells whereas miRNAs that display late differential expression, such as miR-23b, regulates the beating phenotype during in vitro cardiac differentiation from Embryonic Stem Cells (ESCs). This study could have an impact on regenerative medicine since we showed that miR-27b and miR-23b overexpression differentially modify the ESC cell fate towards the cardiac lineage.

The N-Myc oncoprotein induces neuroblastoma, which arises from undifferentiated neuroblasts in the sympathetic nervous system, by modulating gene and protein expression and consequently causing cell differentiation block and cell proliferation. The class IIa histone deacetylase 5 (HDAC5) represses gene transcription, and blocks myoblast, osteoblast and leukemia cell differentiation. Here we showed that N-Myc upregulated HDAC5 expression in neuroblastoma cells. Conversely, HDAC5 repressed the ubiquitin-protein ligase NEDD4 gene expression, increased Aurora A gene expression and consequently upregulated N-Myc protein expression. Genome-wide gene expression analysis and protein co-immunoprecipitation assays revealed that HDAC5 and N-Myc repressed the expression of a common subset of genes by forming a protein complex, whereas HDAC5 and the class III HDAC SIRT2 independently repressed the expression of another common subset of genes without forming a protein complex. Moreover, HDAC5 blocked differentiation

A Comparative Study of Associative Classifiers in Mesenchymal Stem Cell Differentiation Analysis: 10.4018/978-1-60960-067-9.ch011: Discovering how Mesenchymal Stem Cells (MSCs) can be differentiated is an important topic in stem cell therapy and tissue engineering. In a general context

Mesenchymal stem cells (hMSC) represent a small population of cells located in bone marrow and most of the connective tissue. hMSC are multipotent and their ability to differentiate into osteoblast makes them suitable for application in regenerative orthopedics. In this research, I investigated the level of osteogenic differentiation of hMSC after the treatmant with osteoinductive molecules under the standard protocol. In vitro differentiation was evaluated by the analysis of bone markers - alkaline phosphatase and bonesialoprotein and by analysis of markers of stemness. Oct4, Sox2 i Nanog are pluripotency markers of embryonic stem cells but their expression was also confirmed in some types of adult stem cells. The aim of this research was to investigate if they were expressed in hMSC and if their expression decreases during differentiation. Results of RT qPCR showed that Oct4, Sox2 i Nanog are expressed in undifferentiated hMSC and that their expression decreases paralel with the apperance and ...

Human embryonic stem cells (hESC) derived from the inner cell mass of pre-implantation human blastocysts have two unique properties-indefinite self-renewal in culture and pluripotency, or the ability to differentiate into tissues from all three embryonic germ layers. As a result, hESC are a promising source of cells for regenerative medicine applications and have enormous potential in modeling human embryonic development. To realize this potential, a deeper understanding of the basic biology of hESC, especially of the genes that regulate self-renewal and differentiation, will be necessary. ❧ The focus of our study is on Oct4, a POU domain transcription factor and critical regulator of pluripotency whose levels are precisely controlled in mouse embryonic stem cells (mESC). In contrast to the single murine Oct4 isoform, which is better understood and more widely studied, three alternatively spliced isoforms exist in humans-OCT4A, OCT4B, and OCT4B1. Studies of human OCT4 are further confounded by ...

TY - JOUR. T1 - Molecular aspects of lens cell differentiation. AU - Papaconstantinou, John. PY - 1967/1/1. Y1 - 1967/1/1. N2 - I have presented a series of observations on macromolecular interactions which occur during the terminal stages of lens cell differentiation. These are summarized in Fig. 2. Other cell types that undergo similar changes are the erythrocyte and skin cells (epidermis) during the process of keratinization. These other cells are also involved in the synthesis of highly specific proteins, and there are indications that molecular alterations similar to those described for the lens may also occur in these cells (26). Thus, elucidation of a specific series of macromolecular interactions such as those described may provide a basis for the biochemical definition of the terminal stages of cellular differentiation. Differentiation of the reticulocyte, for example, involves inactivation of the nucleus, stabilization of mRNA, and possibly a ribosomal breakdown such as I have ...

Connexin43 (Cx43) is the most widely and abundantly expressed gap junction (GJ) protein and it is strongly associated with the regulation of cell cycle progression. Emerging roles for Cx43 in cell adhesion and migration during neural differentiation have also been recently recognized, and this has emphasized the involvement of Cx43 in different physiological process beyond its role as a GJ protein. In this study, we explore the function of Cx43 in the differentiation of human neural progenitor cells (hNPCs) using viral vectors that mediate the overexpression or knockdown of the protein. Results showed that in the absence of this protein fetal cortex-derived hNPCs differentiated toward a neuronal phenotype at expenses of a glial phenotype. Furthermore, the silencing of Cx43 did not affect hNPC proliferation rate or numbers of apoptotic cells. The increase in the number of neurons was not recapitulated when GJ intercellular communications were pharmacologically blocked, and this suggested that ...

Connexin43 (Cx43) is the most widely and abundantly expressed gap junction (GJ) protein and it is strongly associated with the regulation of cell cycle progression. Emerging roles for Cx43 in cell adhesion and migration during neural differentiation have also been recently recognized, and this has emphasized the involvement of Cx43 in different physiological process beyond its role as a GJ protein. In this study, we explore the function of Cx43 in the differentiation of human neural progenitor cells (hNPCs) using viral vectors that mediate the overexpression or knockdown of the protein. Results showed that in the absence of this protein fetal cortex-derived hNPCs differentiated toward a neuronal phenotype at expenses of a glial phenotype. Furthermore, the silencing of Cx43 did not affect hNPC proliferation rate or numbers of apoptotic cells. The increase in the number of neurons was not recapitulated when GJ intercellular communications were pharmacologically blocked, and this suggested that ...

The Associated Medical Schools of New York (AMSNY) today released a 2012 report showing how New Yorks stem cell program has enabled it to emerge as a leader in stem cell research, and strengthened the states economy through job creation.. This report demonstrates the foresight of New Yorks leaders in funding stem cell research. Not only are scientists across the state making progress towards understanding how to treat or prevent debilitating diseases, New Yorks stem cell program generates jobs, attracts promising young women and men into medical and scientific careers, and enhances our states leadership in biomedical research, said Dr. Lee Goldman, AMSNYs chair, and executive vice president and dean of the Columbia University College of Physicians & Surgeons.. In 2007, New York State allocated $600 million over 11 years to the Empire State Stem Cell Program (NYSTEM), making it the second largest publically-financed stem cell program in the country. To date, New York has awarded nearly ...

Stem cell therapy has revolutionized modern clinical therapy with the potential of stem cells to differentiate into many different cell types which may help to replace different cell lines of an organism. Innumerous trials are carried out to merge new scientific knowledge and techniques with traditional herbal extracts that may result in less toxic, affordable, and highly available natural alternative therapeutics. Currently, mesenchyamal stromal cell (MSC) lines are treated with individual and mixtures of crude herbal extracts, as well as with purified compounds from herbal extracts, to investigate the mechanisms and effects of these on stem cell growth and differentiation. Human MSCs (hMSCs) possess multilineage, i.e., osteogenic, neurogenic, adipogenic, chondrogenic, and myogenic, differentiation abilities. The proliferative and differentiation properties of hMSCs treated with herbal extracts have shown promise in diseases such as osteoporosis, neurodegenerative disorders, and other tissue

In this study, we have identified a novel regulatory function for Jmjd2c at tissue-specific enhancers during ESC priming for differentiation. We show that Jmjd2c is required for successful multi-lineage differentiation, as assessed by EB formation. In the absence of Jmjd2c, EBs were smaller and ineffective at inducing expression of differentiation-associated genes, including early markers of the three mesoderm, endoderm and ectoderm lineages. Moreover, we established that ESC differentiation was impeded or stalled at an early post-implantation epiblast-like stage. Indeed, while Jmjd2c-knockout ESCs could transit into self-renewing cEpiSCs, these cells failed to establish a functionally primed state - a point that was reinforced here by their inability to further progress into mesodermal progenitors. By contrast, we found that Jmjd2c-knockout ESCs could readily differentiate into primitive endoderm-like derivatives under permissive conditions, as recently confirmed in triple Jmjd2abc-knockout ...

TY - JOUR. T1 - Differentiation dependent expression in muscle cells of ZT3, a novel zinc finger factor differentially expressed in embryonic and adult tissues. AU - Polimeni, M.. AU - Giorgi, S.. AU - De Gregorio, L.. AU - Dragani, T. A.. AU - Molinaro, M.. AU - Cossu, G.. AU - Bouché, M.. PY - 1996/1. Y1 - 1996/1. N2 - ZT3, isolated from a murine muscle cell cDNA library by a low-stringency hybridization, encodes a zinc finger domain containing factor with a transcript of 5.0 kb. A 3 2.5 kb partial nucleotide sequence contains an ORF of 1.5 kb where 17 canonical C2H2 zinc finger domains organized in tandem were identified. It maps on mouse chromosome 11, close to two mutations which affect skeletal formation. ZT3 expression depends upon differentiation of myogenic cells in culture, since it is upregulated with myogenin and inhibited in scr-transfected C2C12 cells. ZT3 is not expressed in NIH3T3 or C3H10T1/2 fibroblasts, but is induced when fibroblasts are myogenically converted by ...

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.. ...

TY - JOUR. T1 - 1,25-Dihydroxyvitamin D3 induces human myeloid cell differentiation via the mTOR signaling pathway. AU - Kim, Yongjin. AU - Kim, Hee Suk. AU - Sohn, Jeongwon. AU - Ji, Jong Dae. PY - 2019/11/19. Y1 - 2019/11/19. N2 - 1,25-Dihydroxyvitamin D3 or 1,25(OH)2D3 is known to play an important role in the differentiation of human myeloid cells. However, the molecular mechanism underlying the 1,25(OH)2D3-mediated differentiation of human myeloid cells is incompletely understood. Here, we report that 1,25(OH)2D3 induces differentiation of human myeloid cell lines such as U937 and THP-1 cells via the mammalian target of rapamycin (mTOR) signaling pathway. Both the expression of the differentiation marker CD14 and activation of the mTOR signaling pathway were induced by 1,25(OH)2D3 in phorbol 12-myristate 13-acetate (PMA)-differentiated U937 and THP-1 cells. The 1,25(OH)2D3-induced expression of CD14 in PMA-differentiated U937 and THP-1 cells was prevented by mTOR inhibitors, PP242 and ...

MicroRNAs (miRNAs), small non-coding RNAs, play a critical role in differentiation and self-renewal of pluripotent stem cells, as well as in differentiation of cardiovascular lineage cells. Several miRNAs have been demonstrated to repress stemness factors such as Oct4, Nanog, Sox2 and Klf4 in embryonic stem cells, thereby promoting embryonic stem cell differentiation. Furthermore, targeting of different miRNAs promotes reprogramming towards induced pluripotent stem cells. MicroRNAs are critical for vascular smooth muscle cell differentiation and phenotype regulation, and miR-143 and miR-145 play a particularly important role in this respect. Notably, these miRNAs are down-regulated in several cardiovascular disease states, such as in atherosclerotic lesions and vascular neointima formation. MicroRNAs are critical regulators of endothelial cell differentiation and ischaemia-induced neovascularization. miR-126 is important for vascular integrity, endothelial cell proliferation and ...

I am focusing on the differentiation mechanism of pluripotent stem cells such as ES, iPS cells and germ stem cells with primary emphasis on the establishment of the methods to control their differentiation. My research also includes validation of natural compounds and synthetic chemicals on cell differentiation and carcinogenesis using genetically engineered stem cells. Recent data suggest that adipocyte differentiation can be switched to osteoblast simply using siRNA. This method can be applied for the treatment and prevention of osteoporosis. In addition, we found that environmental chemicals modulate germ cell differentiation and retinoic acid signaling in ES cells. I am also interested in application of stem cell biology towards preservation of endemic species of lake Biwa which is the 3rd-oldest lake in the world. We succeeded to establish cell line from endemic fish (Honmoroko, Gnathopogon caerulescens) and to differentiate functional sperm from spermatogonia in vitro ...

TY - JOUR. T1 - Stem cell-derived cell sheet transplantation for heart tissue repair in myocardial infarction. AU - Guo, Rui. AU - Morimatsu, Masatoshi. AU - Feng, Tian. AU - Lan, Feng. AU - Chang, Dehua. AU - Wan, Feng. AU - Ling, Yunpeng. PY - 2020/1/8. Y1 - 2020/1/8. N2 - Stem cell-derived sheet engineering has been developed as the next-generation treatment for myocardial infarction (MI) and offers attractive advantages in comparison with direct stem cell transplantation and scaffold tissue engineering. Furthermore, induced pluripotent stem cell-derived cell sheets have been indicated to possess higher potential for MI therapy than other stem cell-derived sheets because of their capacity to form vascularized networks for fabricating thickened human cardiac tissue and their long-term therapeutic effects after transplantation in MI. To date, stem cell sheet transplantation has exhibited a dramatic role in attenuating cardiac dysfunction and improving clinical manifestations of heart failure in ...

Individual human embryonic stem cell (hESC) lines often demonstrate a differentiation bias towards a specific germ layer, which may hamper the efficiency of hESC-based biomedical applications. A better understanding of the molecular mechanisms causing this phenomenon is therefore needed. However, an accurate quantification of differentiation bias is challenging, as culture conditions also influence differentiation outcome. Here, we compared standardized methods to quantify definitive endoderm (DE) differentiation potential of four hESC lines. All lines carried a balanced chromosomal content and were cultured in identical conditions on laminin-521TM in NutristemTM medium. First, we used our in-house optimized embryoid body (EB) formation protocol to generate equal-sized EBs, followed by 21-days of spontaneous differentiation in APEL medium. Gene expression analysis did not show a lineage bias between differently sized EBs within the same line, but we detected consistent differences between ...

Primary cultures of stromal-vascular (S-V) cells from adipose tissue were used to investigate the regulation of preadipocyte development. Differentiation of S-V cells was found to be under hormonal control. Insulin and glucocorticoids are essential for S-V cell differentiation in culture. S-V cells from both newborn and mature pig adipose tissue and sera from both ages were used to examine the effect of age on preadipocyte development. S-V cells from newborn pigs replicated faster and appeared more responsive to serum borne factors influencing S-V cell growth and development in culture. Serum source (newborn vs mature) did not affect differentiation of S-V cells from newborn or mature pig adipose tissue. When sera from fed or fasted pigs were used to culture newborn pig S-V cells, fasted pig sera stimulated greater differentiation and decreased cell replication as indicated by DNA content of rat S-V cell culture. Lean pig serum compared to obese pig serum, increased differentiation activity in ...

b,Objective,/b,: To develop an embryoid body-free directed differentiation protocol for the rapid generation of functional vascular endothelial cells derived from human embryonic stem cells (hESCs) and to assess the system for microRNA regulation and angiogenesis.,p,,/p, ,b,Methods and Results,/b,: The production of defined cell lineages from hESCs is a critical requirement for evaluating their potential in regenerative medicine. We developed a feeder- and serum-free protocol. Directed endothelial differentiation of hESCs revealed rapid loss of pluripotency markers and progressive induction of mRNA and protein expression of vascular markers (including CD31 and vascular endothelial [VE]-cadherin) and angiogenic growth factors (including vascular endothelial growth factor), increased expression of angiogenesis-associated microRNAs (including miR-126 and miR-210), and induction of endothelial cell morphological features. In vitro, differentiated cells produced nitric oxide, migrated across a wound, ...

To explore the lineage-specific gene expression changes in those cells, expression levels of SCL, LMO2, and RUNX1 were analyzed. When FLI1 was overexpressed in CD34+ cells, SCL and RUNX1 increased dramatically by tens of folds. Consistently, overexpression of the other narrowed genes showed comparable effects to FLI1, such as HOXA9, MZF1, SOX6, and PCGF2. We then investigated more lineage-specific gene expressions by real-time PCR, including genes involved in erythroid differentiation (KLF1 and EPOR), those in MkP differentiation (FLI1 and GABPA), and those in both lineages (GATA1, NFE2, GATA2, and MYB). Erythroid genes have low expression levels in all of the samples and overexpression of narrowed genes did not lead to significant changes, while the MkP genes were obviously up-regulated in most of the samples (SI Appendix, Fig. S4E).. Stepwise differentiation from HSCs to MkPs included several stages, such as HSCs, multipotent progenitors (MPPs), common myeloid progenitors (CMPs), and MEPs. ...

TY - JOUR. T1 - Overexpression of bcl-2 protein inhibits terminal differentiation of oral keratinocytes in vitro. AU - Harada, Hidemitsu. AU - Mitsuyasu, Takeshi. AU - Seta, Yuji. AU - Maruoka, Yuka. AU - Toyoshima, Kuniaki. AU - Yasumoto, Shigeru. PY - 1998/1. Y1 - 1998/1. N2 - The bcl-2 proto-oncogene is a known inhibitor of apoptosis; in normal human stratified squamous epithelium, its expression is restricted to the basal cell layer. To investigate the functional role of bcl-2 protein in the process of differentiation of oral keratinocytes, bcl-2 expression vector was transfected into SCC-25 cells, which normally undergo squamous cell differentiation in vitro while expressing specific differentiation markers, e.g., keratin 10/11 and involucrin. In bcl-2 transfected SCC-25 cells, the expression of these differentiation markers was markedly suppressed. The bcl-2 proto-oncogene may play a critical role in opposing the commitment to terminal differentiation and apoptosis of oral ...

Although pre-clinical studies in pigs have been performed to improve our understanding of the effects of MSC therapy [15, 16, 35, 36], the characterization of pMSC has lagged behind. The comparison of pMSC with hMSC is necessary to reliably extrapolate pre-clinical data on pMSC therapy, which highly depends on similarities between porcine and human MSC. This is illustrated by the fact that clear differences in murine MSC were found depending on mice strains, required growth media, growth rates and presence of surface epitopes [37]. The expression of markers on pig MSC, and differentiation to osteoblasts, adipocytes and chondrocytes have been described before [38-40]. However, a direct comparison of pMSC with hMSC for all the described MSC features is still lacking.. In our study, we therefore compared the immune-phenotype of pMSC and hMSC, as well as their multi-lineage differentiation potential using various differentiation protocols. Moreover, we demonstrated for the first time that isolation ...

Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (∼80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells. Both female and male LysM-Cre Runx1(fl/fl) mice had decreased trabecular bone mass (72% decrease in bone volume fraction) and increased osteoclast number (2-3 times) (P < .05) without alteration of osteoblast histomorphometric indices. We also demonstrated that loss of Runx1 in ...

The p38 MAPK subfamily is generally activated in response to environmental stresses. In most studies activation of p38 MAPKs, especially p38α isoform ultimately leads to an inflammation or an apoptotic response (30, 31). However, recent studies have shown that activation of p38α also can lead to other biological outcomes such as proliferation, cell survival, and differentiation, depending on the context and the cell type (32-39). Several studies have demonstrated that Epo induces a mitogenic response in hematopoietic cell lines through p38 MAPK pathway (23-25). However, such studies were performed using cell lines that do not recapitulate the normal growth and differentiation program. We investigated the expression, activation, and function of four isoforms of p38 MAPK by using primary erythroid progenitors that terminally differentiate into reticulocytes during in vitro culture. Interestingly, our data show that only p38α and p38γ isoforms are continuously expressed throughout ...

The Cellartis iPS Cell to Hepatocyte Differentiation System generates stable, functional hepatocytes from human induced pluripotent stem cells.

Antibodies for proteins involved in paraxial mesodermal cell fate commitment pathways, according to their Panther/Gene Ontology Classification

Sigma-Aldrich offers abstracts and full-text articles by [M Takasato, P X Er, M Becroft, J M Vanslambrouck, E G Stanley, A G Elefanty, M H Little].

Previously reported that that FTO-knock out mice display postnatal growth retardation, which manifests as reduced body weight and bone mineral density (Guo et al., 2011); however, the molecular mechanism by which FTO stimulates osteogenic differentiation remains unknown. Here, we demonstrate for the first time that FTO stimulates osteogenic differentiation by inducing mild ER stress. The results of the current study illustrate one mechanism underlying the role of FTO in osteogenic differentiation. A relationship between FTO and AMPK has been previously reported (Pitman et al., 2013; Wu et al., 2017). One study demonstrated that AMPK decreases lipid accumulation in skeletal muscle cells by suppressing FTO expression (Wu et al., 2017). Another study revealed that knockdown of FTO reduces phosphorylation of AMPK in Alzheimers disease (Pitman et al., 2013). The current study demonstrated that activation of AMPK markedly increased expression of FTO and that a positive feedback loop existed between ...

Background-The mechanisms underlying the de-differentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast de-differentiation recapitulates the generation of multipotent progenitors during embryonic development which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bi-lineage conversion of fibroblasts via the generation of intermediate progenitors.. Methods-CD34+ progenitors were generated following the de-differentiation of human adult dermal fibroblasts by overexpression of pluripotency transcription factors. Sorted CD34+ cells were transdifferentiated into induced endothelial cells (iECs) and induced erythroblasts (iErythroblasts) using lineage specific growth factors. The therapeutic potential of the generated cells was assessed in an experimental model of myocardial ...

In drug repositioning research, a new concept in drug discovery and new therapeutic opportunities have been identified for existing drugs. Midazolam (MDZ) is an anesthetic inducer used for general anesthesia. Here, we demonstrate the combined effects of bone morphogenetic protein-2 (BMP-2) and MDZ on osteogenic differentiation. An immortalized mouse myoblast cell line (C2C12 cell) was cultured in the combination of BMP-2 and MDZ (BMP-2+MDZ). The differentiation and signal transduction of C2C12 cells into osteoblasts were investigated at biological, immunohistochemical, and genetic cell levels. Mineralized nodules formed in C2C12 cells were characterized at the crystal engineering level. BMP-2+MDZ treatment decreased the myotube cell formation of C2C12 cells, and enhanced alkaline phosphatase activity and expression levels of osteoblastic differentiation marker genes. The precipitated nodules consisted of randomly oriented hydroxyapatite nanorods and nanoparticles. BMP-2+MDZ treatment reduced the

The overexpression of specific gene products via pronuclear injection to create transgenic mice is an established routine protocol. Gain-of-function studies, using ES cells, have also been successfully applied to models of cardiomyogenic differentiation. Grepin et al,28 for example, successfully applied this technique to examine the role of the zinc finger cardiac transcription factor GATA-4 in P19 EC cells. In the absence of cell aggregation, GATA-4 overexpression induced subtle cellular changes, including downregulation of embryonic markers Oct-4 and SSEA-1. With cell aggregation, GATA-4 overexpression led to an increased abundance of mRNAs for transcription factors (Nkx2.5, MLP, and Mhox), contractile proteins (cardiac troponin C and β-MHC), and peptide hormones (brain natriuretic peptide) and accelerated the expression of terminal differentiation markers. Thus, GATA-4 contributes to the differentiation of mesodermal cells, activates the cardiac gene program, and may be a nuclear target for ...

title: Let7a involves in neural stem cell differentiation relating with TLX level, doi: 10.1016/j.bbrc.2015.05.004, category: Article

Embryonic stem (ES) cells are pluripotent cells derived from developing mouse blastocysts in vitro that maintain long‐term self renewal and the capacity to give rise to all cell types in the adult body (including some extraembryonic cell types) when subjected to the appropriate conditions

Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. multipotent adult progenitor cells along mesodermal lineages and exhibited the enhanced expression of alkaline phosphatase and production of calcium-containing mineral debris by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells exhibited enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrixConly control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be ...

BioAssay record AID 80927 submitted by ChEMBL: Compound was tested for differentiation-inducing activity against human promyelocytic leukemia cell line HL-60.

TY - JOUR. T1 - Non-cell autonomous cues for enhanced functionality of human embryonic stem cell-derived cardiomyocytes via maturation of sarcolemmal and mitochondrial K ATP channels. AU - Keung, Wendy. AU - Ren, Lihuan. AU - Sen Li, Li. AU - Wong, Andy On Tik. AU - Chopra, Anant. AU - Kong, Chi Wing. AU - Tomaselli, Gordon F.. AU - Chen, Christopher S.. AU - Li, Ronald A.. PY - 2016/9/28. Y1 - 2016/9/28. N2 - Human embryonic stem cells (hESCs) is a potential unlimited ex vivo source of ventricular (V) cardiomyocytes (CMs), but hESC-VCMs and their engineered tissues display immature traits. In adult VCMs, sarcolemmal (sarc) and mitochondrial (mito) ATP-sensitive potassium (K ATP) channels play crucial roles in excitability and cardioprotection. In this study, we aim to investigate the biological roles and use of sarcK ATP and mitoK ATP in hESC-VCM. We showed that SarcI K, ATP in single hESC-VCMs was dormant under baseline conditions, but became markedly activated by cyanide (CN) or the known ...

The robust and reproducible generation of hepatocytes from iPS cells has enormous implications for basic and clinical research, drug development, and cell-based therapy. The Cellartis iPS to Hepatocyte Differentiation System is a complete system with a universal differentiation protocol to make hepatocytes from various iPS cell lines. It includes the DEF-CS media for maintenance of iPS cells in monolayer culture in order to generate optimal starting material with low spontaneous differentiation and high pluripotency for subsequent differentiation into DE cells and hepatocytes. Our system allows for directed differentiation of 20 different iPS cells resulting in cells with a clear hepatocyte morphology with no residual pluripotent cells. The iPS-derived hepatocytes express markers typical of mature hepatocytes such as HNFα, albumin, PXR, and Phase I metabolizing enzymes. Finally, the iPS cell-derived hepatocytes faithfully recapitulate the metabolic diversity found in the human ...

TY - JOUR. T1 - SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation. AU - Kuroda, Takuya. AU - Yasuda, Satoshi. AU - Tachi, Shiori. AU - Matsuyama, Satoko. AU - Kusakawa, Shinji. AU - Tano, Keiko. AU - Miura, Takumi. AU - Matsuyama, Akifumi. AU - Sato, Yoji. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation propensity. SALL3 expression in hiPSCs correlates positively with ectoderm differentiation capacity and negatively with mesoderm/endoderm differentiation capacity. Without affecting self-renewal of hiPSCs, SALL3 knockdown inhibits ectoderm differentiation and conversely enhances mesodermal/endodermal differentiation. Similarly, loss- and gain-of-function ...

TY - JOUR. T1 - Suppression of histone deacetylation promotes the differentiation of human pluripotent stem cells towards neural progenitor cells. AU - Yang, Juan. AU - Tang, Yu. AU - Liu, Hui. AU - Guo, Fang. AU - Ni, Jun. AU - Le, Weidong. PY - 2014. Y1 - 2014. N2 - Background: Emerging studies of human pluripotent stem cells (hPSCs) raise new prospects for neurodegenerative disease modeling and cell replacement therapies. Therefore, understanding the mechanisms underlying the commitment of neural progenitor cells (NPCs) is important for the application of hPSCs in neurodegenerative disease therapies. It has been reported that epigenetic modifications of histones play important roles in neural differentiation, but the exact mechanisms in regulating hPSC differentiation towards NPCs are not fully elucidated. Results: We demonstrated that suppression of histone deacetylases (HDACs) promoted the differentiation of hPSCs towards NPCs. Application of HDAC inhibitors (HDACi) increased the expression ...

TY - JOUR. T1 - SUMOylation of Blimp-1 is critical for plasma cell differentiation. AU - Ying, Hsia Yuan. AU - Su, Shin Tang. AU - Hsu, Pang Hung. AU - Chang, Che Chang. AU - Lin, I. Ying. AU - Tseng, Yu Hsuan. AU - Tsai, Ming Daw. AU - Shih, Hsiu Ming. AU - Lin, Kuo I.. PY - 2012/7. Y1 - 2012/7. N2 - Transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) is a master regulator of plasma cell differentiation. Here we show that Blimp-1 is covalently modified by SUMO1 at lysine 816, a modification mediated by SUMO E3 ligase PIAS1. Mutation of Blimp-1 lysine 816 reduces transcriptional repression-correlating with a reduced interaction with a histone deacetylase, HDAC2-and impairs differentiation of antibody-secreting cells. Thus, the SUMO pathway critically regulates Blimp-1 function during plasma cell differentiation.. AB - Transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) is a master regulator of plasma cell differentiation. Here we show that ...

In the present study, we aim to elucidate the role of caveolin-1 in modulating astroglial differentiation of neural progenitor cells (NPCs) and the potential mechanisms involved. We first investigated astroglial differentiation and Notch signaling by detecting the expressions of S100β, GFAP, NICD and hairy enhancer of split 1 (Hes1) in the brains of wild-type and caveolin-1 knockout mice. Caveolin-1 knockout mice revealed remarkably less astroglial differentiation and lower levels of NICD and Hes1 expressions than wild type mice. We then studied the potential roles of caveolin-1 in modulating NICD and Hes1 expressions and astroglial differentiation in isolated cultured NPCs by using caveolin-1 peptide and caveolin-1 RNA silencing. In the differentiating NPCs, caveolin-1 peptide markedly promoted astroglial formation and up-regulated the expressions of NICD and Hes1. In contrast, the knockdown of caveolin-1 inhibited astroglial differentiation of NPCs and the expressions of NICD and Hes1. Taken ...

Title:The Role of MicroRNAs in the Pancreatic Differentiation of Pluripotent Stem Cells. VOLUME: 3 ISSUE: 1. Author(s):Natalie Francis, Melanie Moore, Guy A. Rutter and Chris Burns. Affiliation:Endocrinology Section, Biotherapeutics Department, National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK.. Keywords:Differentiation, embryonic stem cells, endoderm, induced pluripotent stem cells, insulin, microRNA, pancreas, type 1 diabetes, type 2 diabetes.. Abstract:The generation of β-cells in vitro is an attractive option for cell therapy treatments for type 1 diabetes and also for the development of more accurate disease models. A number of studies have demonstrated that insulin-expressing cells can be generated by the in vitro differentiation of human pluripotent stem cells. However, to date, these differentiation protocols are often inefficient, time-consuming and highly variable. In many cases, this is a result of an incomplete ...

Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. multipotent adult progenitor cells along mesodermal lineages and exhibited the enhanced expression of alkaline phosphatase and production of calcium-containing mineral debris by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells exhibited enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrixConly control groups. The potent combination of angiogenic and osteogenic properties provided. ...

Objective: The hepatic integration of human adipose tissue derived mesenchymal stem cells (hAT-MSCs) in vivo with or without prior differentiation to hepatocyte-like cells in vitro was investigated.. Methods and results: Cells, isolated either from peritoneal or subcutaneous adipose tissue, expressed mesenchymal stem cell surface markers and featured multiple lineage differentiation. Under conditions favouring hepatocyte differentiation, hAT-MSCs gained hepatocytic functions in vitro including urea formation, glycogen synthesis, cytochrome P450 enzyme activity, and expression of hepatocyte-specific transcripts of carbamoylphosphate synthetase, albumin and cytochrome P450 type 3A4 (CYP3A4). Transgenic expression of green fluorescent protein emerged upon hepatocyte differentiation when driven by the hepatocyte-specific promoter of the cytosolic phosphoenolpyruvate carboxykinase gene but was constitutive from the ubiquitin gene promoter. Human AT-MSCs were transplanted into livers of ...

Purpose : There are several methods for inducing the differentiation of human embryonic stem cells (hESCs) into photoreceptors precursors. Herein, we studied photoreceptors generation in two-dimensional (2D) or a three-dimensional (3D) cell culture model. In addition, we studied the retention of labeled photoreceptor cells in the subretinal space of rats by fluorescence imaging of the retina. Methods : hESCs (H9, US National Stem Cell Bank) differentiation into photoreceptor precursors was investigated in two cell culture models: a 2D model where photoreceptor differentiation was induced in monolayer cultures over 17 days using media including Dkk1, Noggin and IGF1, or a 3D model, where differentiation was induced in suspension cultures over 21 days with media containing endo-IWR 1, SAG, CHIR 99021. Differentiation was studied by immunostaining (CRX, PAX6) and mRNA expression (CRX,VSX2,PAX6). Cells that were subjected to the differentiation protocol were labeled by infection with GFP-expressing ...

Induced pluripotent stem cells (iPSCs) prepared from somatic cells might become a novel therapeutic tool in regenerative medicine, especially for the central nervous system (CNS). In this study, we attempted to induce O4-positive (O4(+)) oligodendrocytes from adult human fibroblast-derived iPSCs in vitro. We used two adult human iPSC cell lines, 201B7 and 253G1. 201B7 was induced by four-gene transduction (oct4, sox2, klf4, c-myc), and 253G1 was induced by three-gene transduction (oct4, sox2, klf4). We treated these cells with two in vitro oligodendrocyte-directed differentiation protocols that were optimized for human embryonic stem cells. One protocol used platelet-derived growth factor as the major mitogen for oligodendrocyte lineage cells, and the other protocol used epidermal growth factor (EGF) as the mitogen. Although the differentiation efficiency was low (less than 0.01%), we could induce O4(+) oligodendrocytes from 253G1 cells using the EGF-dependent differentiation protocol. This is ...

TY - JOUR. T1 - Hhex is Required at Multiple Stages of Adult Hematopoietic Stem and Progenitor Cell Differentiation. AU - Goodings, Charnise. AU - Smith, Elizabeth. AU - Mathias, Elizabeth. AU - Elliott, Natalina. AU - Cleveland, Susan M.. AU - Tripathi, Rati M.. AU - Layer, Justin H.. AU - Chen, Xi. AU - Guo, Yan. AU - Shyr, Yu. AU - Hamid, Rizwan. AU - Du, Yang. AU - Davé, Utpal P.. N1 - Publisher Copyright: © 2015 AlphaMed Press. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2015/8/1. Y1 - 2015/8/1. N2 - Hhex encodes a homeodomain transcription factor that is widely expressed in hematopoietic stem and progenitor cell populations. Its enforced expression induces T-cell leukemia and we have implicated it as an important oncogene in early T-cell precursor leukemias where it is immediately downstream of an LMO2-associated protein complex. Conventional Hhex knockouts cause embryonic lethality precluding analysis of adult hematopoiesis. Thus, we induced highly efficient ...

Primary stem cell-derived endothelial cells can be used for a variety of purposes (e.g., assays of cell-cell adhesion, migration, vascular tube formation, angiogenesis assays and many other applications) Standard biochemical procedures can be performed using endothelial cell cultures include RT-PCR, Western blotting, immunoprecipitation, or immunofluorescent staining or flow cytometry, et al.. Primary stem cell-derived endothelial cells from Cell Biologics are distributed for research purposes only. Our products are not authorized for human use. Transfer or resale of any Cell Biologics cells or products from the purchaser to other markets, organizations, or individuals is prohibited by Cell Biologics without the express written consent of the company. Cell Biologics Terms and Conditions must be accepted before submitting an order.. Question 9: How much does isolation of stem cell-derived endothelial cells cost? ...

Human embryonic stemcells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stemcell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a ...

The present study identifies cAMP‐Erk1/2/p38Mapk‐Creb1 signalling as a functionally important intracellular signalling cascade for CNS remyelination that is regulated at the earliest stages of OPC differentiation. These data complement previous studies demonstrating a role for Erk2 and p38Mapk (Chew et al, 2010) as positive regulators of oligodendrocyte differentiation in vitro and during developmental myelination. Loss of ERK2 attenuates OPC differentiation and leads to a delay but not a complete arrest in the appearance of differentiated oligodendrocytes in vivo (Fyffe‐Maricich et al, 2011). Similarly, p38Mapk inhibition decreases OPC differentiation and Mbp expression without effecting either proliferation or survival (Chew et al, 2010). Reporter assay studies have demonstrated that p38MAPK activity up‐regulates the activity and/or expression of transcription factors that can bind the 2 kb mouse MBP promoter. However, p38MAPK can also antagonize ERK, JNK, c‐Jun phosphorylation. We ...

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

Differentiation of induced pluripotent stem cells (iPSCs) toward hematopoietic progenitor cells (HPCs) raises high hopes for disease modeling, drug screening, and cellular therapy. Various differentiation protocols have been established to generate iPSC-derived HPCs (iHPCs) that resemble their primary counterparts in morphology and immunophenotype, whereas a systematic epigenetic comparison was yet elusive. In this study, we compared genome-wide DNA methylation (DNAm) patterns of iHPCs with various different hematopoietic subsets. After 20 days of in vitro differentiation, cells revealed typical hematopoietic morphology, CD45 expression, and colony-forming unit (CFU) potential. DNAm changes were particularly observed in genes that are associated with hematopoietic differentiation. On the other hand, the epigenetic profiles of iHPCs remained overall distinct from natural HPCs. Furthermore, we analyzed if additional co-culture for 2 weeks with syngenic primary mesenchymal stromal cells (MSCs) or iPSC

Louis Jun Ye Ong, Lor Huai Chong, Lin Jin, Pawan Kumar Singh, Poh Seng Lee, Hanry Yu, Abhishek Ananthanarayanan, Hwa Liang Leo, Yi-Chin Toh. The practical application of microfluidic liver models for in vitro drug testing is partly hampered by their reliance on human primary hepatocytes, which are limited in number and have batch-to-batch variation. Human stem cell-derived hepatocytes offer an attractive alternative cell source, although their 3D differentiation and maturation in a microfluidic platform have not yet been demonstrated. We develop a pump-free microfluidic 3D perfusion platform to achieve long-term and efficient differentiation of human liver progenitor cells into hepatocyte-like cells (HLCs). The device contains a micropillar array to immobilize cells three-dimensionally in a central cell culture compartment flanked by two side perfusion channels. Constant pump-free medium perfusion is accomplished by controlling the differential heights of horizontally orientated inlet and outlet ...

Objective To explore the role of Nrf2/EZH2 in mediating erythroid differentiation in mouse erythroleukemia cells under DMSO exposure. Methods MEL cells were treated with DMSO. Erythroid differentiation was detected by bezidine staining. The expression levels of Nrf2 and EZH2 were determined by western blotting. Results DMSO induced erythroid differentiation in MEL cells,along with significant induction of Nrf2 and EZH2 expression. TBHQ,a selective Nrf2 activator,increased the protein level of Nrf2.Interestingly,TBHQ also induced EZH2 expression. The lentiviral particle containing Nrf2 short hairpin RNA( shRNA) efficiently blocked TBHQ-induced EZH2 levels. Moreover,Nrf2 or EZH2 shRNA significantly inhibited DMSO-induced erythroid differentiation. Conclusion Nrf2 induction is involved in MELerythroid differentiation under DMSO exposure by regulating EZH2.

TY - JOUR. T1 - Combined introduction of Bmi-1 and hTERT immortalizes human adipose tissue-derived stromal cells with low risk of transformation. AU - Tátrai, Péter. AU - Szepesi, Áron. AU - Matula, Zsolt. AU - Szigeti, Anna. AU - Buchan, Gyöngyi. AU - Mádi, András. AU - Uher, Ferenc. AU - Német, Katalin. PY - 2012/5/25. Y1 - 2012/5/25. N2 - Adipose tissue-derived stromal cells (ASCs) are increasingly being studied for their usefulness in regenerative medicine. However, limited life span and donor-dependent variation of primary cells such as ASCs present major hurdles to controlled and reproducible experiments. We therefore aimed to establish immortalized ASC cell lines that provide steady supply of homogeneous cells for in vitro work while retain essential features of primary cells. To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs. The resulting cell lines ASC ...

mesenchymal stem cell differentiation involved in metanephric nephron morphogenesis - Ontology Report - Chinchilla Research Resource Database

Objective: Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs).The present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs),but also describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl4)-induced liver inflammation model.Methods: Undifferentiated hESCs were treated with Rho-associated kinase (ROCK) inhibitor and induced to fibroblast-looking cells.These cells were tested for their surface markers and multilineage differentiation capability.Further more,we analyzed their immune characteristics by mixed lymphocyte reactions (MLRs) and animal experiments.Results: hESC-MSCs show a homogenous fibroblastic morphology that resembles bone marrow-derived MSCs (BM-MSCs).The cell markers and differentiation potential of hESC-MSCs are also similar to those of BM-MSCs.Unlike their original cells,hESC-MSCs possess poor immunogenicity and can

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Pluripotent stem cells have the ability to differentiate into all cell and tissue types of the body, most notably shown in mice by the generation of chimeric animals. Directed differentiation of human pluripotent stem cells into various cell types in vitro has only recently become possible by applying developmental signals based on lessons learned from developmental biology in animals. Initial attempts to generate beta cells from human embryonic stem cells relied on spontaneous differentiation. By culturing embryonic bodies in stem cell media, Assady and colleagues reported the upregulation of insulin transcripts and occasional insulin‐positive cells, but most cells were not of pancreatic origin (Assady et al, 2001). To improve differentiation efficiency into insulin‐positive cells, developmental steps were sequentially targeted, progressing from definitive endoderm to primitive gut tube, through posterior foregut, pancreatic endoderm, pancreatic endocrine progenitors and, finally, to beta ...

TY - CONF. T1 - Mechanical control of stem cell differentiation using microengineered matrix. AU - Fu, Jianping. AU - Wang, Yang-Gao. AU - Yang, Michael T.. AU - Lee, Ted T.. AU - Chen, Christopher S.. PY - 2008/1/1. Y1 - 2008/1/1. N2 - In this work, we explore the molecular mechanisms by which local mechanical properties (e.g., rigidity) of the extracellular matrix (ECM) cooperates with soluble cues to regulate lineage commitment of human mesenchymal stem cells (hMSCs). We have established different micropost array substrates that can definitively decouple matrix rigidity from other properties including adhesiveness. We applied these substrates to investigate the influences of matrix rigidity on cell adhesion, cytoskeleton assembly/contractility, cell spreading, and proliferation. We further show that matrix rigidity regulates commitment of hMSCs to either adipogenic or osteogenic fate: soft matrix facilitates adipogenic differentiation while stiff matrix proves osteogenic.. AB - In this work, ...

Satellite cells are skeletal muscle progenitor/stem cells that reside between the basal lamina and plasma membranes of skeletal fibers in vivo. These cells can give rise to both myogenic and adipogenic cells. Given the possible role for differentiation of satellite cells into adipocytes in marbling and in some pathological disorders like sarcopenia, knowledge of the proteins involved in such process remains obscure. Using two-dimensional polyacrylamide gel electrophoresis coupled with mass spectrometry, we investigated the proteins that are differentially expressed during adipogenic differentiation of satellite cells from bovine longissimus muscle. Our proteome mapping strategy to identify the differentially expressed intracellular proteins during adipogenic differentiation revealed a total of 25 different proteins. The proteins up-regulated during adipogenic differentiation of satellite cells like Cathepsin H precursor, Retinal dehydrogenase 1, Enoyl-CoA hydratase, Ubiquinol-cytochrome-c ...

Video articles in JoVE about multipotent stem cells include Isolation of Blood-vessel-derived Multipotent Precursors from Human Skeletal Muscle, Isolation of Neural Stem/Progenitor Cells from the Periventricular Region of the Adult Rat and Human Spinal Cord, Production and Administration of Therapeutic Mesenchymal Stem/Stromal Cell (MSC) Spheroids Primed in 3-D Cultures Under Xeno-free Conditions, Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues, A cGMP-applicable Expansion Method for Aggregates of Human Neural Stem and Progenitor Cells Derived From Pluripotent Stem Cells or Fetal Brain Tissue, Manual Isolation of Adipose-derived Stem Cells from Human Lipoaspirates, Isolation of Perivascular Multipotent Precursor Cell Populations from Human Cardiac Tissue, Visualization and Quantification of Mesenchymal Cell Adipogenic Differentiation Potential with a Lineage Specific Marker, In Vitro Pancreas Organogenesis from Dispersed Mouse

Merck and Plasticell of London, UK, today announced the availability of OsteoMAX-XF™, the first fully defined, xeno-free human mesenchymal stem cell differentiation medium for the differentiation of mesenchymal stem cells into osteocytes.

Highly aggressive, metastatic and therapeutically resistant triple-negative breast cancers (TNBCs) are often enriched for cancer stem cells (CSC). Cytokines within the breast tumor microenvironment (TME) influence the CSC state by regulating tumor cell differentiation programs. Two prevalent breast TME cytokines are oncostatin-M (OSM) and interferon-β (IFN-β). OSM is a member of the IL-6 family of cytokines and can drive the de-differentiation of TNBC cells to a highly aggressive CSC state. Conversely, IFN-β induces the differentiation of TNBC, resulting in the repression of CSC properties. Here, we assess how these breast TME cytokines influence CSC plasticity and clinical outcome. Using transformed human mammary epithelial cell (HMEC) and TNBC cell models, we assessed the CSC markers and properties following exposure to OSM and/or IFN-β. CSC markers included CD24, CD44, and SNAIL; CSC properties included tumor sphere formation, migratory capacity, and tumor initiation. There are three major

TY - JOUR. T1 - Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Hepatocytes. AU - Basma, Hesham E. AU - Soto-Gutiérrez, Alejandro. AU - Yannam, Govardhana Rao. AU - Liu, Liping. AU - Ito, Ryotaro. AU - Yamamoto, Toshiyuki. AU - Ellis, Ewa. AU - Carson, Steven D. AU - Sato, Shintaro. AU - Chen, Yong. AU - Muirhead, David. AU - Navarro-Álvarez, Nalu. AU - Wong, Ronald J.. AU - Roy-Chowdhury, Jayanta. AU - Platt, Jeffrey L.. AU - Mercer, David F. AU - Miller, John D.. AU - Strom, Stephen C.. AU - Kobayashi, Naoya. AU - Fox, Ira J.. PY - 2009/3. Y1 - 2009/3. N2 - Background & Aims: The ability to obtain unlimited numbers of human hepatocytes would improve the development of cell-based therapies for liver diseases, facilitate the study of liver biology, and improve the early stages of drug discovery. Embryonic stem cells are pluripotent, potentially can differentiate into any cell type, and therefore could be developed as a source of human hepatocytes. Methods: To generate ...

The term embryoid body has been broadly applied to describe pluripotent cell aggregates induced to differentiate using a variety of different formation and culture methods. Generally, an aggregate of pluripotent stem cells, cultured in suspension, and capable of forming derivatives of all three germ lineages is regarded as an EB. Although no universally accepted benchmarks currently exist for EB formation, characteristics such as EB size, shape, and homogeneity are typically used as points of reference for comparison. Common EB culture practices, such as hanging drop and static suspension culture were adopted from in vitro differentiation methods originally used for embryonic carcinoma (EC) cells, pluripotent precursors to the ESCs themselves.37 A comprehensive review describing several of the most common EB culture methods has recently been published.38. The hanging drop method of EB formation produces homogeneous cell aggregates by dispensing a defined number of ESCs in physically separated ...

Memory B cells (MBCs) are key for protection from reinfection. However, it is mechanistically unclear how germinal center (GC) B cells differentiate into MBCs. MYC is transiently induced in cells fated for GC expansion and plasma cell (PC) formation, so-called positively selected GC B cells. We found that these cells coexpressed MYC and MIZ1 (MYC-interacting zinc-finger protein 1 [ZBTB17]). MYC and MIZ1 are transcriptional activators; however, they form a transcriptional repressor complex that represses MIZ1 target genes. Mice lacking MYC-MIZ1 complexes displayed impaired cell cycle entry of positively selected GC B cells and reduced GC B cell expansion and PC formation. Notably, absence of MYC-MIZ1 complexes in positively selected GC B cells led to a gene expression profile alike that of MBCs and increased MBC differentiation. Thus, at the GC positive selection stage, MYC-MIZ1 complexes are required for effective GC expansion and PC formation and to restrict MBC differentiation. We propose that ...

Stem cell encapsulation technology demonstrates much promise for the replacement of damaged tissue in several diseases, including spinal cord injury (SCI). The use of biocompatible microcapsules permits the control of stem cell fate in situ to facilitate the replacement of damaged/lost tissue. In this work, a novel customized microfluidic device was developed for the reproducible encapsulation of neural stem cells (NSCs) and dental pulp stem cells (DPSCs) within monodisperse, alginate-collagen microcapsules. Both cell types survived within the microcapsules for up to 21 days in culture. Stem cells demonstrated retention of their multipotency and neuronal differentiation properties upon selective release from the microcapsules, as demonstrated by high proliferation rates and the production of stem cell and neuronal lineage markers. When cell-laden microcapsules were transplanted into an organotypic SCI model, the microcapsules effectively retained the transplanted stem cells at the site of ...

Recent studies suggest that ovarian germ line stem cells replenish oocyte-pool in adult stage, and challenge the central doctrine of fixed germ cell pool in mammalian reproductive biology. Two distinct populations of spherical stem cells with high nucleo-cytoplasmic ratio have been recently identified in the adult mammalian ovary surface epithelium (OSE) including nuclear OCT-4A positive very small embryonic-like (VSELs) and cytoplasmic OCT-4 expressing ovarian germ stem cells (OGSCs). Three weeks culture of scraped OSE cells results in spontaneous differentiation of the stem cells into oocyte-like, parthenote-like, embryoid body-like structures and also embryonic stem cell-like colonies whereas epithelial cells attach and transform into a bed of mesenchymal cells. Present study was undertaken, to further characterize ovarian stem cells and to comprehend better the process of spontaneous differentiation of ovarian stem cells into oocyte-like structures in vitro. Ovarian stem cells were enriched by

TY - JOUR. T1 - Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro. AU - Trakarnsanga, Kongtana. AU - Wilson, Marieangela C.. AU - Heesom, Kate J.. AU - Andrienko, Tatyana N.. AU - Srisawat, Chatchawan. AU - Frayne, Jan. PY - 2018/1/31. Y1 - 2018/1/31. N2 - Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, the numbers produced fall short of that required for therapeutics, due to limited proliferative capacity of the erythroblasts. To overcome this hurdle, approaches are required to increase the expansion potential of such culture systems. The OP9 mouse stromal cell line is known to promote haematopoietic differentiation of pluripotent stem cells, however an effect of OP9 cells on erythropoiesis has not been ...

Adult human male germ cell tumors are unique in their display of histopathologies that resemble different stages of human development, and thus comprise a model system for the study of molecular mechanisms involved in human ES3 cell development (1) . Cell lines derived from such tumors, in particular, EC, have provided an invaluable in vitro resource in which molecular events regulating cell fate/lineage decision can be studied (2) . The EC cell lines can be maintained in an undifferentiated state in vitro, and undergo spontaneous or morphogen-induced differentiation programs. Some display the ability to differentiate along both somatic and extra-embryonic lineages placing them as equivalents of cells in the inner cell mass of the developing embryo (3 , 4) , whereas others exhibit a more restricted pluripotential differentiation program (5 , 6) . Global perspectives of the expression patterns of such cell lines during different differentiation programs may lead to the identification of genes ...

TY - JOUR. T1 - Cellular therapeutics for heart failure. T2 - Focus on mesenchymal stem cells. AU - Pandey, Amitabh C.. AU - Lancaster, Jordan J.. AU - Harris, David T.. AU - Goldman, Steven. AU - Juneman, Elizabeth. PY - 2017. Y1 - 2017. N2 - Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF) manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs) have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of ...

TY - THES. T1 - Study of endocrine markers involved in dedifferentiation and identification of C function or redifferentiate pancreatic β-cells in type 2 diabetes. AU - Neelankal John, Abraham. PY - 2018. Y1 - 2018. N2 - To enhance the knowledge of β-cell dedifferentiation (BCD) and its causal role in Type 2 diabetes (T2D), my studies employed β-cell line mouse insulinoma 6 (MIN6) and db/db islets from T2D model mice thereby establishing those as models of dedifferentiation. Vitamin D receptor (VDR)-targeted therapy that employed LCA propionate was utilized to treat early passage MIN6 and db/+ mice islets in the pre-diabetic state to protect β-cell from undergoing dedifferentiation. Furthermore, my research using MIN6 and db/db also identified a novel druggable compound ANJR12947285, which has the potential to induce redifferentiation in dedifferentiated β-cell. AB - To enhance the knowledge of β-cell dedifferentiation (BCD) and its causal role in Type 2 diabetes (T2D), my studies employed ...

In the present study, we found that AS-BMSCs showed normal proliferation, cell viability, surface markers and multiple differentiations characteristics, but significantly reduced immunomodulation potential; also, the frequencies of Treg and Fox-P3+ cells in AS-PBMCs decreased, but CCR4+CCR6+ Th cells increased. Moreover, the AS-BMSCs induced the ratio of CCR4+CCR6+ Th/Treg cell imbalance when co-cultured with PBMCs. Additionally, no differences were found between HD1 and HD2. Impressively, the immunomodulation potential of BMSCs has negative correlation with the ratios of CCR4+CCR6+ Th to Treg cells in peripheral blood.. Characteristic symptoms of AS are spinal stiffness, ankylosis and syndesmophytes [1], which are explained by spinal inflammation, structural damage, or both [40]. As the ankylosis of the spine or even spinal stiffness was probably initiated by the heterotopic ossification of osteoblasts, and most of these osteoblasts derived from BMSCs [41, 42], and, simultaneously, there were ...

All-trans retinoic acid (ATRA), a biologically active metabolite of vitamin A, is a powerful inducer of terminal differentiation and growth arrest of several myeloid cell lines in vitro. Although the efficacy of ATRA as an anti-cancer drug has been demonstrated by the successful treatment of acute promyelocytic leukemia (APL), knowledge concerning the molecular mechanisms directing ATRA-induced differentiation and cell cycle arrest of myeloid cells is lacking. Our results show, for the first time, that the complex regulation of cell cycle proteins and myeloid-specific transcription factors induced by ATRA relies on functional Stat1. We found that Stat1 is activated by both tyrosine-701 and serine-727 phosphorylation upon ATRA-induced differentiation of the human monoblastic cell line U-937. Expression of phosphorylation deficient mutants of Stat1 (Stat1Y701F or Stat1S727A) inhibited both ATRA-induced differentiation and cell cycle arrest of U-937 cells, pointing to a requirement of active Stat1 ...

Human stem cells, both embryonic and induced pluripotent stem cells, offer exciting opportunities for cell-based therapies in injured or diseased human brains or spinal cords. The clinical efficacy of grafted progenitor cells critically depends on their ability to migrate to the appropriate sites in the adult central nervous system without unwanted proliferation and tumor formation. However, little is known about the cellular behavior of human neural progenitor cells derived from human stem cells or how their proliferation and migration are coordinated. During this reporting period, we continued to study human neural progenitor cells derived from human stem cells, a cell culture system established during the prior reporting period. We focused on microRNAs, a class of small, noncoding RNAs of ~21-23 nucleotides that regulate gene expression at the posttranscriptional level. These small RNAs mostly destabilize target mRNAs or suppress their translation by binding to complementary sequences in the ...

Development of long-lived humoral immunity is dependent on CXCR5-expressing T follicular helper (Tfh) cells, which develop concomitantly to effector Th cells that support cellular immunity. Conventional dendritic cells (cDCs) are critical APCs for initial priming of naive CD4+ T cells but, importantly, also provide accessory signals that govern effector Th cell commitment. To define the accessory role of cDCs during the concurrent development of Tfh and effector Th1 cells, we performed high-dose Ag immunization in conjunction with the Th1-biased adjuvant polyinosinic:polycytidylic acid (pI:C). In the absence of cDCs, pI:C failed to induce Th1 cell commitment and IgG2c production. However, cDC depletion did not impair Tfh cell differentiation or germinal center formation, and long-lived IgG1 responses of unaltered affinity developed in mice lacking cDCs at the time point for immunization. Thus, cDCs are required for the pI:C-driven Th1 cell fate commitment but have no crucial accessory function ...

Scientists produce functioning neurons from human embryonic stem cells Neurons will be used to create models of neurological diseases. Thursday, 09 August 2007 Scientists with the Institute of Stem Cell Biology and Medicine at UCLA were able to produce from human embryonic stem cells a highly pure, large quantity of functioning neurons that will allow them to create models of and study diseases such as Alzheimers, Parkinsons, prefrontal dementia and schizophrenia. Researchers previously had been able to produce neurons - the impulse-conducting cells in the brain and spinal cord - from human embryonic stem cells. However, the percentage of neurons in the cell culture was not high and the neurons were difficult to isolate from the other cells. UCLAs Yi Sun, an associate professor of psychiatry and biobehavioral sciences, and Howard Hughes Medical Institute investigator Thomas Südhof at the University of Texas Southwestern Medical Center were able to produce 70 to 80 percent of neurons in cell ...

Gap junctions (GJs) are intercellular channels connecting the cytoplasm of adjacent cells. This type of connection is an efficient way of cellular communications in many tissues including the central nervous system. Connexins are the proteins that constitute mammalian GJs, and Connexin43 (Cx43) is the most abundant isoform expressed in body cells. Cx43 has been detected within immature neural populations, but only in astrocytes in the adult brain and investigations have shown that Cx43 channel and adhesive properties largely influence neuronal differentiation of mouse neural progenitor (NP) cells. To date the role of Cx43 in neuronal differentiation remains unexplored in human systems, hence our study aimed to investigate the Cx43 participation in human NP differentiation. We largely detected Cx43 protein within the immature neural populations showing that protein expression occurred by fibroblast growth factor (FGF _2) stimulation through the ERKlj2 pathway; FGF _2 withdrawal induced NP ...

Important tool in understanding differentiation in hESCs Wednesday, 24 October 2007 Researchers know very little about how human embryonic stem cells (hESC) self-renew. To fully understand these cells self renewal capacity and pluripotency, and their regulation, it is necessary to efficiently generate genetically modified cells and analyze the consequences of elevated and reduced expression of genes. Researchers at the University of Minnesotas Stem Cell Institute have described how an existing genetic tool can be used to study how human embryonic stem cells differentiate. The research appears in the November 2007 issue of Experimental Biology and Medicine. The research team, led by the University of Minnesotas Meri Firpo, Ph.D., included gene therapy researchers at Los Angeles Childrens Hospital, and developmental biologists at the University of Michigan. The researchers used knockdown technology to reduce the expression of oct4, a gene known to be necessary for self renewal of mouse and ...