TY - JOUR. T1 - Mechanistic contribution of ubiquitous 15-lipoxygenase-1 expression loss in cancer cells to terminal cell differentiation evasion. AU - Moussalli, Micheline J.. AU - Wu, Yuanqing. AU - Zuo, Xiangsheng. AU - Yang, Xiu L.. AU - Wistuba, Ignacio Ivan. AU - Raso, Maria G.. AU - Morris, Jeffrey S.. AU - Bowser, Jessica L.. AU - Minna, John D.. AU - Lotan, Reuben. AU - Shureiqi, Imad. PY - 2011/12. Y1 - 2011/12. N2 - Loss of terminal cell differentiation promotes tumorigenesis. 15-Lipoxygenase-1 (15-LOX-1) contributes to terminal cell differentiation in normal cells. The mechanistic significance of 15-LOX-1 expression loss in human cancers to terminal cell differentiation suppression is unknown. In a screen of 128 cancer cell lines representing more than 20 types of human cancer, we found that 15-LOX-1 mRNA expression levels were markedly lower than levels in terminally differentiated cells. Relative expression levels of 15-LOX-1 (relative to the level in terminally differentiated ...
TY - JOUR. T1 - Krüppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids. AU - Yoshida, Tadashi. AU - Gan, Qiong. AU - Owens, Gary K.. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2008/11. Y1 - 2008/11. N2 - Phenotypic switching of vascular smooth muscle cells (SMCs), such as increased proliferation, enhanced migration, and downregulation of SMC differentiation marker genes, is known to play a key role in the development of atherosclerosis. However, the factors and mechanisms controlling this process are not fully understood. We recently showed that oxidized phospholipids, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), which accumulate in atherosclerotic lesions, are potent repressors of expression of SMC differentiation marker genes in cultured SMCs as well as in rat carotid arteries in vivo. Here, we examined the molecular mechanisms ...
Involucrin (Squamous Cell Terminal Differentiation Marker) Antibody - Without BSA and Azide, Mouse Monoclonal Antibody [Clone SY5 ] validated in IHC-P, IF, FC (AH10541-100), Abgent
Wright N.; Morley A.; Appleton D., 1971: The effect of testosterone on cell differentiation and proliferation in the castrate mouse small intestine
The use of human induced pluripotent stem cell-derived neural progenitor cells (hiPSC-NPCs) is an attractive therapeutic option for damaged nerve tissues. To direct neuronal differentiation of stem cells, we have previously developed an electrospun polycaprolactone nanofiber scaffold that was functionalized with siRNA targeting Re-1 silencing transcription factor (REST), by mussel-inspired bioadhesive coating. However, the efficacy of nanofiber-mediated RNA interference on hiPSC-NPCs differentiation remains unknown. Furthermore, interaction between such cell-seeded scaffolds with injured tissues has not been tested. In this study, scaffolds were optimized for REST knockdown in hiPSC-NPCs to enhance neuronal differentiation. Specifically, the effects of two different mussel-inspired bioadhesives and transfection reagents were analyzed. Scaffolds functionalized with RNAiMAX Lipofectamine-siREST complexes enhanced the differentiation of hiPSC-NPCs into TUJ1+ cells (60% as compared to 22% in ...
Notch2 interaction with its ligand, Dll1, is required in the mouse to drive MZP into the MZB cell lineage (Saito et al., 2003; Hozumi et al., 2004). Preliminary data based on humanized mouse models have also proposed a Notch2 dependence for the differentiation of IgM+IgD+CD27+ B cells (Scheeren et al., 2008). Accordingly, we searched for an MZP in the spleen from young children, taking as diagnostic criteria its capacity to acquire an MZ phenotype when cultured in presence of OP9 cells expressing human DLL1, a differentiation which, moreover, should be specifically inhibited in presence of anti-NOTCH2 blocking antibodies. This precursor subset was identified using the recently described MEM55 antibody, which marks a glycosylated variant of the CD45RB molecule, harbored by CD27+ B cells and an immature B cell subset (Koethe et al., 2011). Surprisingly, these MZPs were further characterized as expressing the ABCB1 transporter reported so far as the unique hallmark of naive B cells (Wirths and ...
The process of generating hiPS cell-derived hepatocytes begins with the directed differentiation of hiPS cells into definitive endoderm (DE) cells, which are then differentiated further into hepatocytes. The complete system provides media, supplements, and coating reagents for each step of the hiPS-cell-to-hepatocyte differentiation protocol. Starting with approximately 3 x 106 undifferentiated hiPS cells, this system yields 5 x 106 hepatocytes-equivalent to a confluent monolayer of 50 cm2. Importantly, this do-it-yourself system offers a solution for the consistent production of assay-ready cells from patient-derived cells, or from Cellartis brand iPS cell lines-enabling highly reproducible results.. Successful differentiation depends on the quality of the starting material; a homogeneous, undifferentiated stem cell population is ideal. The iPS Cell to Hepatocyte Differentiation System promotes high-quality starting material by incorporating DEF-CS culture system components, which are designed ...
Renovos OPC differentiation assay is used to identify compounds that promote the production of oligodendrocytes from OPCs. In this assay, OPCs are cultured with or without compounds in differentiation media in 96-well plates. Following 5 days of differentiation, cells are stained and imaged in high-content ArrayScan™ reader in multiple channels. Computer algorithms are used to quantify the number of viable and pyknotic cells, and the number of EGFP+ oligodendrocytes in each well of the plate. Immunostaining of additional markers of different cell types can also be performed and quantified.. Applications of the OPC differentiation assay include:. ...
Glioma differentiation therapy is a novel strategy that has been used to induce glioma cells to differentiate into glia-like cells. Although some advances in experimental methods for exploring the molecular mechanisms involved in differentiation therapy have been made, a model-based comprehensive analysis is still needed to understand these differentiation mechanisms and improve the effects of anti-cancer therapeutics. This type of analysis becomes necessary in stochastic cases for two main reasons: stochastic noise inherently exists in signal transduction and phenotypic regulation during targeted therapy and chemotherapy, and the relationship between this noise and drug efficacy in differentiation therapy is largely unknown. In this study, we developed both an additive noise model and a Chemical-Langenvin-Equation model for the signaling pathways involved in glioma differentiation therapy to investigate the functional role of noise in the drug response. Our model analysis revealed an ultrasensitive
Background: The role of mesenchymal stem cell in cellular therapy is the subject of interest for many researchers. The differentiation potential of MSCs and abilities in modulations of the recipients immune system makes them important cells in tissue regenerative studies. MSCs by releasing the proinflammatory cytokines play important role in immunomodulatory systems; however the signaling pathways for releasing of these mediators are not well understood. Glutathione has been shown to play a role in modulation of cytokines in hepatogenic differentiation. Objective: In the current study we aimed to investigate the effects of buthionine sulfoximine (BSO, inhibitor for glutathione synthesis) and N-acetylecystin (NAC, an inhibitor for ROS generation) on proinflammatory cytokines production in a hepatogenic differentiation model. Results: BSO and NAC significantly decreased IL-6 and TNF-α levels at 14 days of differentiation, whereas, NAC decreased the levels of IL-8 at days 2 and 14 of differentiation.
The development of tumor cell differentiation agents is new initiative in cancer treatment research. The goal of this project was to identify breast cancer differentiation agents by screening quinoline ring-containing compounds obtained form National Cancer Institute Compound Library. Of six differentiation-inducing quinolines NSC3852 was chosen as a lead compound. Our results demonstrate that NSC3852 is an inhibitor of HDAC activity in HeLa and MCF-7 cells nuclear extracts. NSC3852 caused superoxide generation in MCF-7 cells in a NADPH oxidase-dependent fashion, and NSC3852-induced oxidative stress led to the shift in a redox potential of the cells to a more oxidized state. This change in redox status of the cells was accompanied by the accumulation of hypophosphorylated pRb, downregulation of E2F-1 and Myc transcription factor protein levels, and cell differentiation. Superoxide formation in response to NSC3852 exposure caused DNA damage and subsequently apoptosis. MCF-7 cells growth was inhibited.
Background: We have previously shown that knockout of E2F1 in mice enhances angiogenesis following induction of hind limb ischemia. Recent studies suggest that suppression of E2F1 enhances oxidative phosphorylation in a variety of cell types. Since an increase in oxidative phosphorylation in stem/progenitor cells is often associated with cell differentiation, we hypothesize that E2F1-deficiency may promote bone marrow (BM) progenitor cell differentiation thereby impact on ischemic cardiac repair.. Methods and Results: We cultured bone marrow (BM) Lin- progenitor cells under hypoxic and normxic conditions for 24 h, then measured the expression of metabolism associated genes and evaluated cell proliferation and differentiation. We also performed adoptive BM transplantation to reconstitute BM of WT mice with E2F1-/- or WT BM, followed by surgical induction of myocardial infarction (MI), to compare the role of BM E2F1 in the cardiac repair in vivo. Notably, we found that the expression levels of ...
Bcl6 is required for CD4 T cell differentiation into T follicular helper cells (Tfh). In this study, we examined the role of IL-6 in early processes of in vivo Tfh differentiation, because the timing and mechanism of action of IL-6 in Tfh differentiation have been controversial in vivo. We found that early Bcl6(+)CXCR5(+) Tfh differentiation was severely impaired in the absence of IL-6; however, STAT3 deficiency failed to recapitulate that defect. IL-6R signaling activates the transcription factor STAT1 specifically in CD4 T cells. Strikingly, we found that STAT1 activity was required for Bcl6 induction and early Tfh differentiation in vivo. IL-6 mediated STAT3 activation is important for downregulation of IL-2Rα to limit Th1 cell differentiation in an acute viral infection. Thus, IL-6 signaling is a major early inducer of the Tfh differentiation program unexpectedly mediated by both STAT3 and STAT1 transcription factors. ...
Analysis of MM14 mouse myoblasts demonstrates that terminal differentiation is repressed by pure preparations of both acidic and basic fibroblast growth factor (FGF). Basic FGF is approximately 30-fold more potent than acidic FGF and it exhibits half maximal activity in clonal assays at 0.03 ng/ml (2 pM). FGF repression occurs only during the G1 phase of the cell cycle by a mechanism that appears to be independent of ongoing cell proliferation. When exponentially growing myoblasts are deprived of FGF, cells become postmitotic within 2-3 h, express muscle-specific proteins within 6-7 h, and commence fusion within 12-14 h. Although expression of these three terminal differentiation phenotypes occurs at different times, all are initiated by a single regulatory commitment event in G1. The entire population commits to terminal differentiation within 12.5 h of FGF removal as all cells complete the cell cycle and move into G1. Differentiation does not require a new round of DNA synthesis. Comparison ...
TY - JOUR. T1 - Stomach Organ and Cell Lineage Differentiation. T2 - From Embryogenesis to Adult Homeostasis. AU - Willet, Spencer G.. AU - Mills, Jason C.. PY - 2016/1/1. Y1 - 2016/1/1. N2 - Gastric diseases cause considerable worldwide burden. However, the stomach is still poorly understood in terms of the molecular-cellular processes that govern its development and homeostasis. In particular, the complex relationship between the differentiated cell types located within the stomach and the stem and progenitor cells that give rise to them is significantly understudied relative to other organs. In this review, we highlight the current state of the literature relating to specification of gastric cell lineages from embryogenesis to adulthood. Special emphasis is placed on substantial gaps in knowledge about stomach specification that we think should be tackled to advance the field. For example, it has long been assumed that adult gastric units have a granule-free stem cell that gives rise to all ...
Nurr1, a transcription factor belonging to the nuclear receptor family, is essential for the generation of midbrain dopamine (DA) cellsduring embryonic development and it continues to be expressed in adult DA neurons. However, the mechanism by which Nurr1 promotes dopamine cell differentiation has remained unknown. In this study, I have used a neuronal progenitor cell line (NT2/D1), which retains some stem cell characteristics and is capable only of terminal differentiation into neurons, to analyze the function of Nurr1 in dopamine cell development. The results demonstrated that Nurr1 can induce cell cycle arrest and the cells differentiated with distinct neuronal morphology after all-trans retinoic acid treatment. It was also indicated that up-regulation of some dopaminergic neuron markers (e.g. TH, DAT and D2DR) while down-regulation of CyclinD1-Cdk6 activity marks the key events in the early stages of dopaminergic neuron differentiation. Furthermore, Pin1, a highly conserved isomerase, which ...
Background: MiR-499 is a cardiac-abundant miRNA. However, the biological functions of miR-499 in differentiated cardiomyocytes or in the cardiomyocyte differentiation process is not very clear. Sox6 is believed to be one of its targets, and is also believed to play a role in cardiac differentiation. Therefore, our aim was to investigate the association between Sox6 and miR-499 during cardiac differentiation.. Methodology/Principal Findings: Using a well-established in vitro cardiomyocyte differentiation system, mouse P19CL6 cells, we found that miR-499 was highly expressed in the late stage of cardiac differentiation. In cells stably transfected with miR-499 (P-499 cells), it was found that miR-499 could promote the differentiation into cardiomyocytes at the early stage of cardiac differentiation. Notably, cell viability assay, EdU incorporation assay, and cell cycle profile analysis all showed that the P-499 cells displayed the distinctive feature of hyperplastic growth. Further investigation ...
Terminal B cell differentiation is a complex process currently modeled upon the actions of a small number of master regulators, and the gaps in our understanding are clear. Insight into the mechanism of differentiation, both its initiation and its full execution, is advanced with the identification of each new contributing factor.. Here, we identify Zbtb20 as a new mediator of B cell differentiation specifically expressed in B1 and GC B cells and ASCs. Zbtb20 is a BTB-ZF transcription factor, and other members of the family have been shown to be active within the B cell lineage (Chevrier and Corcoran, 2014). For instance, early B lineage commitment is mediated by LRF, Bcl6, and Miz-1 (Maeda et al., 2007; Duy et al., 2010; Kosan et al., 2010), MZ B cell differentiation is controlled by LRF (Sakurai et al., 2011), and the GC reaction is driven by Bcl6 and LRF (Fukuda et al., 1997; Sakurai et al., 2011). Finally, Zbtb32 has been associated with plasma cell differentiation (Yoon et al., ...
TY - JOUR. T1 - Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic β-cell-derived components. AU - Oh, Ju Eun. AU - Choi, Ok Kyung. AU - Park, Ho Seon. AU - Jung, Hye Seung. AU - Ryu, Su Jeong. AU - Lee, Yong Deok. AU - Lee, Seung Ah. AU - Chung, Sung Soo. AU - Choi, Eun Young. AU - Lee, Dong Sup. AU - Gho, Yong Song. AU - Lee, Hakmo. AU - Park, Kyong Soo. PY - 2019/3/29. Y1 - 2019/3/29. N2 - Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) ...
negative regulation of anterior neural cell fate commitment of the neural plate by fibroblast growth factor receptor signaling pathway - Ontology Report - Rat Genome Database
Characterizing genes associated with leukemic cell differentiation may provide help for understanding mechanisms on the leukemia differentiation. The aim of this study is to investigate whether the expression of melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) could be induced during leukemia differentiation and whether mda-7/IL-24 plays a role in leukemia differentiation. We showed that the expression of mda-7/IL-24 and IL-24 delE5, an mda-7/IL-24 splice variant, was induced in U937 and HL60 cells during 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated monocytic differentiation. Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway was required for their induction. Knockdown of mda-7/IL-24 and IL-24 delE5 resulted in significant inhibition of the monocytic differentiation induced by TPA. More importantly, ectopic overexpression of mda-7/IL-24 and IL-24 delE5 significantly induced U937 cells, HL60 cells, and blast cells from ...
In this directed differentiation protocol, Pax3-GFP is overexpressed in mesenchymal stem cells via viral transduction. After infection, cells are subjected to fluorescence-activated cell sorting (FACS) to isolate the GFP-positive cells. Isolated cells are cultured in mesenchymal stem cell expansion medium without growth factors, to promote their differentiation into myogenic cells. The differentiated cells are multinucleated and express early-myogenic markers ...
Directed differentiation is a bioengineering methodology at the interface of stem cell biology, developmental biology and tissue engineering. It is essentially harnessing the potential of stem cells by constraining their differentiation in vitro toward a specific cell type or tissue of interest. Stem cells are by definition pluripotent, able to differentiate into several cell types such as neurons, cardiomyocytes, hepatocytes, etc. Efficient directed differentiation requires a detailed understanding of the lineage and cell fate decision, often provided by developmental biology. During differentiation, pluripotent cells make a number of developmental decisions to generate first the three germ layers (ectoderm, mesoderm and endoderm) of the embryo and intermediate progenitors, followed by subsequent decisions or check points, giving rise to all the bodys mature tissues. The differentiation process can be modeled as sequence of binary decisions based on probabilistic or stochastic models. ...
The present studies were undertaken to determine whether the CDKI FP could enhance PMA-induced maturation in human leukemia cells. The rationale for this investigation stemmed from several considerations: (a) FP has been shown to induce differentiation in some cell types (e.g., non-small cell lung cancer cells; Ref. 21 ); and (b) inhibition of cell cycle progression by FP might promote a leukemic cell differentiation program (47) . Contrary to expectations, coexposure to FP for 24 h strikingly opposed PMA-induced differentiation in U937 cells and instead significantly increased apoptosis. These events were associated with increased mitochondrial dysfunction, activation of caspases, and loss of clonogenic survival; moreover, enhanced cell death after PMA/FP cotreatment was also observed in promyelocytic leukemia cells (HL-60) and in U937 cells overexpressing the antiapoptotic protein Bcl-2. These events may reflect the complex reciprocal relationship that exists between differentiation and ...
Supplementary MaterialsSupplementary Info Supplementary Numbers 1-3, Supplementary Furniture 1-5 and Supplementary References ncomms9487-s1. ducts that drain alveoli during lactation. The nature of the stem cell(s) that maintain this epithelium is definitely controversial. Initial transplantation experiments using purified cell subsets shown that only the basal cells experienced the potential to regenerate ductalClobular outgrowths or engrafting capacity colony-forming cells (CFCs) in the luminal compartment can also be recognized: Sca1?CD49b+ luminal progenitors (termed Sca1? progenitors) that express low levels of luminal cell differentiation markers and Sca1+CD49b+ luminal progenitors (termed Sca1+ progenitors) that express high levels of luminal cell differentiation markers3,8,9,10. Analogous luminal cell subpopulations have also been recognized in the human being mammary epithelium, as EpCAM+CD49f? NCL cells, ALDH+EpCAM+CD49f+ luminal progenitors that communicate low levels of luminal ...
The coordination of cell proliferation with the gradual differentiation of different cell types is essential for proper development and tissue homeostasis. However, little is known about the signals that couple cell cycle exit to differentiation switch during development. Here, we show that signaling mediated by integrins, the major cell-ECM receptors, contributes to the regulation of this switch in the posterior follicle cells of the Drosophila ovary. Furthermore, our experiments strongly suggest that one of the mechanisms by which integrins regulate epithelial cell differentiation is by modulating the activity of the Notch pathway through promoting the proper endosomal trafficking and/or processing of Notch.. Integrins are known to regulate cell differentiation and proliferation in other systems. The effects of particular integrins in regulating differentiation vary depending on the epithelial cell type. Thus, although β1 integrin signaling is inhibitory for differentiation in the epidermis ...
Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of the mammalian blastocyst. Cellular differentiation entails loss of pluripotency and gain of lineage-specific characteristics. However, the molecular controls that govern the differentiation process remain poorly understood. We have characterized small RNA expression profiles in differentiating ES cells as a model for early mammalian development. High-throughput 454 pyro-sequencing was performed on 19-30 nt RNAs isolated from undifferentiated male and female ES cells, as well as day 2 and 5 differentiating derivatives. A discrete subset of microRNAs (miRNAs) largely dominated the small RNA repertoire, and the dynamics of their accumulation could be readily used to discriminate pluripotency from early differentiation events. Unsupervised partitioning around meloids (PAM) analysis revealed that differentiating ES cell miRNAs can be divided into three expression clusters with highly contrasted accumulation patterns. ...
© 2012 John Wiley & Sons, Ltd. Stem cell interactions through paracrine cell signalling can regulate a range of cell responses, including metabolic activity, proliferation and differentiation. Moving towards the development of optimized tissue-engineering strategies with adipose-derived stem cells (ASCs), the focus of this study was on developing indirect co-culture models to study the effects of mature adipocytes, chondrocytes and osteoblasts on bovine ASC multilineage differentiation. For each lineage, ASC differentiation was characterized by histology, gene expression and protein expression, in the absence of key inductive differentiation factors for the ASCs. Co-culture with each of the mature cell populations was shown to successfully induce or enhance lineage-specific differentiation of the ASCs. In general, a more homogeneous but lower-level differentiation response was observed in co-culture as compared to stimulating the bovine ASCs with inductive differentiation media. To explore the role of
Bromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell cycle associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation we have looked for Brd2 interacting proteins upon induction of neuronal differentiation. Surprisingly, we have identified the growth factor Pleiotrophin (Ptn). Ptn antagonizes the cell cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduces neuronal differentiation. Ptn-mediated antagonism of Brd2 has been assessed in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis ...
Antibodies for proteins involved in positive regulation of smooth muscle cell differentiation pathways, according to their Panther/Gene Ontology Classification
Adipose stem cells (ASCs) are pluripotent cells with the ability of self-renewal and differentiation into various kinds of mesenchymal cells. a three-dimensional tradition. 10 and 20 M doses of Res demonstrated probably the most proliferating influence on ADSCs. The SIRT 1 genes manifestation and FRAP level also more than doubled set alongside the control group (3D tradition was the right condition for ASCs differentiation to chondrocyte, and lower dosages of Res exert proliferation influence on ASCs. gene manifestation.25,26 The purpose of the present research was to research the result of Res on differentiation of ASCs into chondrocyte in 3D tradition also to evaluate cell success, apoptosis, total antioxidants gene and capacity expression. Strategies and Components With this experimental research, subcutaneous adipose cells had been taken from individuals (20-40 years) during liposuction inside a sterile phosphate-buffered saline (PBS) remedy. The adipose cells were cut into small pieces and ...
Upon activation, naive CD8 T cells undergo a program of proliferation and differentiation that results in the acquisition of effector functions. Optimal T cell activation requires the integration of multiple signals including cross-linking of the T cell receptor (signal 1), co-stimulation (signal 2) and soluble factors such as cytokines (signal 3). Once a CD8 T cell has received these three signals they differentiate into an effector cell, which are able to control infection by directly killing the infected cell. Once the infection is cleared, these effector cells contract by controlled cell death and a long-lived population of memory cells remain. These potent memory cells are the defining feature of adaptive immunity as they offer protection for the life of the host due to their unique capabilities to survive in the absence of antigen and respond rapidly to secondary challenge. Therefore, effective CD8 T cell memory is the goal of cell-mediated vaccination strategies. While it is well ...
Definition of Cell differentiation in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is Cell differentiation? Meaning of Cell differentiation as a legal term. What does Cell differentiation mean in law?
Hematopoietic stem cells (HSC)3 must choose between self-renewal and differentiation; if they differentiate they can become common myeloid progenitors (CMP) or common lymphoid progenitors (CLP). It is still unclear how environmental signals (1) and lineage-specific transcription factors work together to control the frequency with which dividing HSC either undergo self-renewal or commit to one or the other lineage. Transcription factors expressed in HSC can drive commitment to either the lymphoid or the myeloid lineage (2). For example, factors of the Ikaros family specifically favor differentiation down the lymphoid pathway (3), whereas other factors, such as GATA-1 and C/EBPα, favor differentiation down the myeloid pathway (4, 5).. We are particularly interested in mechanisms that influence the choice between self-renewal and differentiation. Thus we study the E2F family of transcription factors, which promotes cell cycle progression and exit; the latter is associated with terminal ...
Due to the pivotal role of stem cell differentiation in regeneration and disease cure, the study of it has always been a research highlight during the recent years. Stress microenvironment has a great impact on cell growth, proliferation, differentiation and apoptosis. Twist1, as a core epithelial-mesenchymal transition (EMT) regulatory factor, plays an important role in these processes. Moreover, Twist1 gene can express in alveolar bone - periodontal ligament interface and the expression can be regulated by changes in the occlusal force. In this article, we will present a review of Twist1 gene, especially in the aspect of the biological functions in stem cell differentiation under mechanical signals and explore whether Twist1 involved in tissue remodeling in alveolar bone - periodontal membrane interface under stress ...
Due to the pivotal role of stem cell differentiation in regeneration and disease cure, the study of it has always been a research highlight during the recent years. Stress microenvironment has a great impact on cell growth, proliferation, differentiation and apoptosis. Twist1, as a core epithelial-mesenchymal transition (EMT) regulatory factor, plays an important role in these processes. Moreover, Twist1 gene can express in alveolar bone - periodontal ligament interface and the expression can be regulated by changes in the occlusal force. In this article, we will present a review of Twist1 gene, especially in the aspect of the biological functions in stem cell differentiation under mechanical signals and explore whether Twist1 involved in tissue remodeling in alveolar bone - periodontal membrane interface under stress ...
The key advantage of iPS cells over other stem cells is that they are patient-specific (and therefore immuno-compatible) and can be grown in infinite amounts. Moreover, they are not dogged by the ethical and religious controversies associated with hES cells, yet still have the same properties as hES cells. They also offer the possibility of conducting clinical-trials-in-the-dish, providing a platform for drug screening, disease modelling and gene/cell therapy in pre-clinical studies.3,4. How are iPS cells made?. When cell differentiation occurs, the cell follows a process of changes in gene activity whereby embryonic-specific genes are inactivated and differentiation-specific genes are activated. The end result of this differentiation programme is a specialised cell of one type or another (e.g. cardiac muscle cells or neurons). To reprogramme a fully differentiated adult cell into an iPS cell is surprisingly straightforward - all that is needed is reactivation of the embryonic regulatory ...
The results presented here demonstrate that the luminal cell compartment in both the human and mouse mammary glands is much more heterogeneous than initially perceived since progenitors of varying levels of luminal cell differentiation can be identified and prospectively isolated. In the mouse, these populations resolve as separable ER+ and ER- subpopulations, whereas in the human the ALDH+ and ALDH- subpopulations appear to comprise a larger contiguous population. The cell types of the different species appear to be homologous to one another; for example, the ER- LPs in the mouse are equivalent to the ALDH+ cells in the human, and likewise for the ER+ luminal mouse progenitors and the ALDH- luminal human progenitor cells because both populations collectively express higher levels of luminal cell differentiation markers than the ER-/ALDH+ subpopulations. The ER+ cells in the mouse are probably ductal-restricted progenitors since they express higher levels of ER and FoxA1, transcription factors ...
We have shown in this study that activation of the canonical Wnt pathway promoted, and inhibition of this pathway blocked, neuronal differentiation both in cortical NPC cultures and in the developing neocortex. We emphasize two aspects of these findings: (1) Wnts appear to function as an extracellular cue that instructively triggers neuronal differentiation; and (2) this effect of Wnts is dependent on the stage of development. In this Discussion, we address these aspects and their possible underlying mechanisms.. In general, two models can explain how the fate of an uncommitted precursor cell is influenced by extrinsic cues. In one model, extrinsic cues instruct multipotent precursor cells to commit to a particular lineage. In the other model, multipotent precursor cells choose their fate stochastically, and the proliferation and/or survival of specific lineage-restricted cells is then supported by extrinsic cues. For example, Pdgf treatment increases the size of the neuronal population in ...
We have found that β-catenin signaling and neural differentiation of ES cells are inhibited by culture at high density. This observation is consistent with prior studies of neural/neuronal differentiation of ES cells that have all used relatively low densities irrespective of whether EB or dissociated cell culture techniques were used (Gratsch and OShea, 2002; Ying et al., 2003). The need to culture the cells at low density to achieve neuronal differentiation limits the number of cells that could potentially be obtained for transplantation strategies and raises questions about the mechanisms mediating neuronal differentiation of the cells. Our studies suggest that β-catenin signaling promotes both neural and neuronal differentiation of ES cells, and that the effects of increased cell density are mediated at least in part by inhibition of β-catenin signaling.. Similar to observations with keratinocytes (Dietrich et al., 2002), culture of ES cells at high density promotes membrane localization ...
Reduction of Prep1 Levels Affects Differentiation of Normal and Malignant B Cells and Accelerates Myc Driven Lymphomagenesis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
AIMS: Cyclin-dependent kinase inhibitors (CDKIs) play a critical role in negatively regulating the proliferation of cardiomyocytes, although their role in cardiac differentiation remains largely undetermined. We have shown that the most prominent CDKI in Xenopus, p27(Xic1)(Xic1), plays a role in neuronal and myotome differentiation beyond its ability to arrest the cell cycle. Thus, we investigated whether it plays a similar role in cardiomyocyte differentiation. METHODS AND RESULTS: Xenopus laevis embryos were sectioned, and whole-mount antibody staining and immunofluorescence studies were carried out to determine the total number and percentage of differentiated cardiomyocytes in mitosis. Capped RNA and/or translation-blocking Xic1 morpholino antisense oligonucleotides (Xic1Mo) were microinjected into embryos, and their role on cardiac differentiation was assessed by in situ hybridization and/or PCR. We show that cell-cycling post-gastrulation is not essential for cardiac differentiation in ...
The adult mammalian dermis contains a subpopulation of precursor cells that possess the capacity to differentiate into different lineages (16-18). These fibroblastic MSCs have attracted attention for their plasticity and, therefore, their potential therapeutic applications, including in transplantation for bone formation (19). In the present study, the role of BMP7 in the osteogenic differentiation of CD105+ hDDFCs was examined in vitro and in vivo, and the underlying Smad-dependent and -independent mechanisms were identified.. Conflicting reports exist on the differentiation potential of dermal fibroblasts, with certain studies suggesting limited potential and others demonstrating adipocytic, osteocytic and chondrocytic differentiation capacities (20-23). One reason for these controversial results is the heterogeneity of isolated dermal fibroblasts, which include populations with different differentiation capacities (5,13). Although dermal fibroblasts have a surface antigen profile similar to ...
NKT cells are potent regulatory T cells that prevent the development of several autoimmune diseases. Analysis of NKT cell regulatory function in the NOD mouse has revealed that NKT cells inhibit the development of type 1 diabetes by impairing the differentiation of anti-islet T cells into Th1 effector cells. In the present study, we have performed in vitro and in vivo experiments to determine the respective role of cytokines and cell contacts in the blockade of T cell differentiation by NKT cells. These experiments reveal that cytokines such as IL-4, IL-10, IL-13, and TGF-beta, that have been involved in other functions of NKT cells, play only a minor role if any in the blockade of T cell differentiation by NKT cells. Diabetes is still prevented by NKT cells in the absence of functional IL-4, IL-10, IL-13, and TGF-beta. In contrast, we show for the first time that cell contacts are crucial for the immunoregulatory function of NKT cells.
GATA-6, a zinc finger transcription factor, is important in the endodermal differentiation of organ tissues.[4] It is also indicated in proper lung development by controlling the late differentiation stages of alveolar epithelium and aquaporin-5 promoter activation. Furthermore, GATA-6 has been linked to the production of LIF, a cytokine that encourages proliferation of endodermal embryonic stem cells and blocks early epiblast differentiation. If left unregulated in the developing embryo, this cytokine production and chemical signal contributes to the phenotypes discussed further below.[5] Upon the disruption of GATA-6 in an embryo, the distal lung epithelial development is stunted in transgenic mice models[4] The progenitor cells, or stem cells, for alveolar epithelial tissues develop and are specified appropriately, however further differentiation does not occur. Also the distal-proximal bronchiole development is affected, resulting in a reduced quantity of airway exchange sites.[4] This ...
Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and ...
Set of osteoblast-inducer reagents, including hydrocortisone, ß-glycerophosphate, and ascorbic acid. These reagents induce the efficient differentiation of bone marrow-derived cells and adipose-derived stem cells (mesenchymal stem cells) into osteoblasts.
BACKGROUND: Human embryonic stem cells (hESCs) offer a virtually unlimited source of neural cells for structural repair in neurological disorders, such as stroke. Neural cells can be derived from hESCs either by direct enrichment, or by isolating specific growth factor-responsive and expandable populations of human neural stem cells (hNSCs). Studies have indicated that the direct enrichment method generates a heterogeneous population of cells that may contain residual undifferentiated stem cells that could lead to tumor formation in vivo. METHODS/PRINCIPAL FINDINGS: We isolated an expandable and homogenous population of hNSCs (named SD56) from hESCs using a defined media supplemented with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and leukemia inhibitory growth factor (LIF). These hNSCs grew as an adherent monolayer culture. They were fully neuralized and uniformly expressed molecular features of NSCs, including nestin, vimentin and radial glial markers. These hNSCs did ...
TY - JOUR. T1 - Eomesodermin controls a unique differentiation program in human IL-10 and IFN-γ coproducing regulatory T cells. AU - Gruarin, Paola. AU - Maglie, Stefano. AU - De Simone, Marco. AU - Häringer, Barbara. AU - Vasco, Chiara. AU - Ranzani, Valeria. AU - Bosotti, Roberto. AU - Noddings, Johanna S. AU - Larghi, Paola. AU - Facciotti, Federica. AU - Sarnicola, Maria L. AU - Martinovic, Martina. AU - Crosti, Mariacristina. AU - Moro, Monica. AU - Rossi, Riccardo L. AU - Bernardo, Maria E. AU - Caprioli, Flavio. AU - Locatelli, Franco. AU - Rossetti, Grazisa. AU - Abrignani, Sergio. AU - Pagani, Massimiliano. AU - Geginat, Jens. N1 - © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.. PY - 2018/11/15. Y1 - 2018/11/15. N2 - Whether human IL-10-producing regulatory T cells (Tr1) represent a distinct differentiation lineage or an unstable activation stage remains a key unsolved issue. Here, we report that Eomesodermin (Eomes) acted as a lineage-defining transcription factor in human ...
The development of skeletal muscle is a multistep process in which pluripotent mesodermal cells give rise to myoblasts that subsequently withdraw from the cell cycle and differentiate into myotubes.2,13 These stages are controlled by the MyoD and myocyte enhancer factor 2 (MEF2) families of transcription factors, which interact with one another to establish a unique transcriptional code for activation of skeletal muscle-specific genes.14 It has been shown that such muscle differentiation-specific gene expression occurs in a stereotype pattern. Within 24 hours of switching to differentiation medium or serum withdrawal, proliferating myoblasts initiate the expression of myogenin, followed by the expression of MEF2 family of transcription factors, including MEF2D.15 Consistent with these observations, we showed in the present study that cell cycle withdrawal induced myogenin and MEF2D protein expression, peaking at 48 and 72 hours after medium switch, respectively. Furthermore, we demonstrated, for ...