Generation of functional eggs from pluripotent stem cells in culture would have impacts on reproductive biology and regenerative medicine. We have recently established a novel culture system in which mouse pluripotent stem cells differentiate to mature oocytes in a manner similar to oogenesis in ...
TY - JOUR. T1 - Epigenetic Silencing of the Key Antioxidant Enzyme Catalase in Karyotypically Abnormal Human Pluripotent Stem Cells. AU - Konki, Mikko. AU - Pasumarthy, Kalyan. AU - Malonzo, Maia. AU - Sainio, Annele. AU - Valensisi, Cristina. AU - Söderström, Mirva. AU - Emani, Maheswara Reddy. AU - Stubb, Aki. AU - Närvä, Elisa. AU - Ghimire, Bishwa. AU - Laiho, Asta. AU - Järveläinen, Hannu. AU - Lahesmaa, Riitta. AU - Lähdesmäki, Harri. AU - Hawkins, R. David. AU - Lund, Riikka J.. PY - 2016/2/25. Y1 - 2016/2/25. N2 - Epigenomic regulation is likely to be important in the maintenance of genomic integrity of human pluripotent stem cells, however, the mechanisms are unknown. We explored the epigenomes and transcriptomes of human pluripotent stem cells before and after spontaneous transformation to abnormal karyotypes and in correlation to cancer cells. Our results reveal epigenetic silencing of Catalase, a key regulator of oxidative stress and DNA damage control in abnormal cells. Our ...
TY - JOUR. T1 - Defining early hematopoietic-fated primitive streak specification of human pluripotent stem cells by the orchestrated balance of Wnt, activin, and BMP signaling. AU - Shen, Jun. AU - Lyu, Cuicui. AU - Zhu, Yaoyao. AU - Feng, Zicen. AU - Zhang, Shuo. AU - Hoyle, Dixie L.. AU - Ji, Guangzhen. AU - Brodsky, Robert A. AU - Cheng, Tao. AU - Wang, Zack Z.. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Distinct regions of the primitive streak (PS) have diverse potential to differentiate into several tissues, including the hematopoietic lineage originated from the posterior region of PS. Although various signaling pathways have been identified to promote the development of PS and its mesoderm derivatives, there is a large gap in our understanding of signaling pathways that regulate the hematopoietic fate of PS. Here, we defined the roles of Wnt, activin, and bone morphogenetic protein (BMP) signaling pathways in generating hematopoietic-fated PS from human pluripotent stem cells (hPSCs). We found ...
en] Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew indefinitely, while maintaining the capacity to differentiate into all cell types of the nervous system. While human pluripotent cell-based therapies are unlikely to arise soon, these cells can currently be used as an inexhaustible source of committed neurons to perform high-throughput screening and safety testing of new candidate drugs. Here, we describe critically the available methods and molecular factors that are used to direct the differentiation of hES or hiPS into specific neurons. In addition, we discuss how the availability of patient-specific hiPS offers a unique opportunity to model inheritable neurodegenerative diseases and untangle their pathological mechanisms, or to validate drugs that would prevent the onset or the progression of these neurological disorders ...
Read "Expression patterns of germ line specific genes in mouse and human pluripotent stem cells are associated with regulation of ground and primed state of pluripotency, Russian Journal of Developmental Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
TY - JOUR. T1 - CXCR2 and its related ligands play a novel role in supporting the pluripotency and proliferation of human pluripotent stem cells. AU - Jung, Ji Hye. AU - Lee, Seung Jin. AU - Kim, Jihea. AU - Lee, Songhee. AU - Sung, Hwa Jung. AU - An, Jungsuk. AU - Park, Yong. AU - Kim, Byung Soo. PY - 2015/4/15. Y1 - 2015/4/15. N2 - Basic fibroblast growth factor (bFGF) is a crucial factor sustaining human pluripotent stem cells (hPSCs). We designed this study to search the substitutive factors other than bFGF for the maintenance of hPSCs by using human placenta-derived conditioned medium without exogenous bFGF (hPCCM-), containing chemokine (C-X-C motif) receptor 2 (CXCR2) ligands, including interleukin (IL)-8 and growth-related oncogene α (GROα), which were developed on the basis of our previous studies. First, we confirmed that IL-8 and/or GROα play independent roles to preserve the phenotype of hPSCs. Then, we tried CXCR2 blockage of hPSCs in hPCCM- and verified the significant decrease ...
Culture conditions play an important role in regulating the genomic integrity of Human Pluripotent Stem Cells (HPSCs). We report that HPSCs cultured in Essential 8 (E8) and mTeSR, two widely used media for feeder-free culturing of HPSCs, had many fold higher levels of ROS and higher mitochondrial potential than cells cultured in Knockout Serum Replacement containing media (KSR). HPSCs also exhibited increased levels of 8-hydroxyguanosine, phospho-histone-H2a.X and p53, as well as increased sensitivity to γ-irradiation in these two media. HPSCs in E8 and mTeSR had increased incidence of changes in their DNA sequence, indicating genotoxic stress, in addition to changes in nucleolar morphology and number. Addition of antioxidants to E8 and mTeSR provided only partial rescue. Our results suggest that it is essential to determine cellular ROS levels in addition to currently used criteria i.e. pluripotency markers, differentiation into all three germ layers and normal karyotype through multiple ...
Laminin α5 substrates promote survival, network formation and functional development of human pluripotent stem cell-derived neurons in ...
Recorded during the ISSCR 2017 Innovation Showcase in Boston, this tutorial highlights human pluripotent stem cell (hPSC) gene-editing and cardiac differentiation workflows using the CloneR™ supplement and the STEMdiff™ Cardiomyocyte System. This talk is
A lot of optimism and promise surrounds the use of human pluripotent stem cells (hPSCs) for applications in regenerative medicine and drug discovery. However, technical challenges still hamper the culturing and differentiation ...
Pluripotent stem cells are known to display distinct metabolic phenotypes than their somatic counterparts. While accumulating studies are focused on the roles of glucose and amino acid metabolism in facilitating pluripotency, little is known regarding the role of lipid metabolism in regulation of stem cell activities. Here, we show that fatty acid (FA) synthesis activation is critical for stem cell pluripotency. Our initial observations demonstrated enhanced lipogenesis in pluripotent cells and during cellular reprogramming. Further analysis indicated that de novo FA synthesis controls cellular reprogramming and embryonic stem cell pluripotency through mitochondrial fission. Mechanistically, we found that de novo FA synthesis regulated by the lipogenic enzyme ACC1 leads to the enhanced mitochondrial fission via (i) consumption of AcCoA which affects acetylation‐mediated FIS1 ubiquitin-proteasome degradation and (ii) generation of lipid products that drive the mitochondrial dynamic equilibrium ...
Heng, J.-C.D., Loh, K.M., Ng, H.-H. (2012-01). Investigating the bona fide differentiation capacity of human pluripotent stem cells. Cell Research 22 (1) : 6-8. [email protected] Repository. https://doi.org/10.1038/cr. ...
Since the first discovery that human pluripotent stem cells (hPS cells) can differentiate to cardiomyocytes, efforts have been made to optimize the conditions under which this process occurs
Focal adhesions are known as signalling platforms broadcasting the information of the biochemical and physical qualities of the extracellular matrix into intracellular signalling cascades. However, focal adhesions remain unstudied in the context of human pluripotent stem cells. The research group led by Academy Professor Johanna Ivaska from the Turku Bioscience Centre at the University of Turku unveiled the ultrastructure of focal adhesion scaffold using state-of-the-art super-resolution microscopy in collaboration with the world-renowned Howard Hughes Medical Institutes Janelia Research Campus.
Influence of Donor Age on Induced Pluripotent Stem Cells To explore the impact of age on iPSC quality, investigators produced induced pluripotent stem cells (iPSCs) from blood cells of 16 donors aged 21-100. They found that iPSCs from older donors retain an epigenetic signature of age, which can be reduced through passaging. Clonal expansion via reprogramming also enables the discovery of somatic mutations present in individual donor cells, which are missed by bulk sequencing methods. [Nat Biotechnol] Abstract Self-Organized Amniogenesis by Human Pluripotent Stem Cells in a Biomimetic Implantation-Like Niche Scientists report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. They showed that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical ...
In this application note from Miltenyi, neural differentiation towards either neural crest (NC) or neural stem cells (NSC) is optimised. A magnetic cell separation protocol to standardise quality and number of true pluripotent stem cells before inducing neural differentiation is developed.
One of the ultimate goals in Regenerative Medicine is the generation of pluripotent stem cells (PSCs) directly from somatic cells obtained from patients. Although major findings in the defini
The gold standard human pluripotent stem cells, embryonic and induced pluripotent stem cells have self-renewal uncontrolled capacity which often materializes in teratoma formation. A novel population of human pluripotent stem cells derived from adipose tissue (AT), termed Multilineage Differentiating Stress Enduring (Muse) (Muse-AT cells) was recently introduced to the scientific community, offering a resolution to the teratogenesis issue that plague ES and iPS cells. Muse-AT have self-renew capacity in a controlled manner without forming teratomas when injected into immune-deficient mice. Muse-AT cells are obtained from lipoaspirate material without the need of genetic manipulation nor the use of cell sorting techniques. Muse-AT cells express classic pluripotency markers and differentiate into cells from the three embryonic germ layers both spontaneously and under media-specific induction. Muse-AT cells exist in a quiescent state under normal physiological circumstances within the cellular ...
Kidneys are the most commonly transplanted organs, but demand far outweighs supply. While the human kidney does have the capacity to repair itself after injury, it is not able to regenerate new nephrons, the individual functional units that make up the kidney. Human pluripotent stem cells are the only human cells we can grow in the laboratory with the potential to generate new functional kidney tissue. Previously, researchers have been able to differentiate pluripotent stem cells into heart, liver, pancreas, or nerve cells by adding certain chemicals, but it has been challenging to turn these stem cells into kidney. Using normal kidney development as a roadmap, we developed the most efficient method for converting human pluripotent stem cells into kidney stem cells that will give rise to nearly all the functional cells of the kidney. These kidney stem cells organize into mature kidney structures that resemble the structures found in a normal human kidney. This gives us hope that, one day, we ...
Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive ...
This protocol describes a method to generate smooth muscle-like cells (SMLCs) from human embryonic stem cells and induced pluripotent stem (iPS) cells. The SMLCs are further cultured in low-serum medium for 18 days to generate contractile SMLCs (Con-SMLCs). Contractile cells mimic the native state of vascular smooth muscle cells (vSMCs) found in vessel walls. When SMLCs are cultured in high-serum medium in the presence of TGFb and PDFG-BB for 18 days, they differentiate into "synthetic" smooth muscle cells, termed Syn-SMLCs. Compared to Syn-SMLCs, Con-SMLCs have a reduced proliferation rate, increased contractile phenotype, numerous and active caveolae with enlarged endoplasmic reticulum and abundant stress fibers and bundles. When transplanted subcutaneously, Con-SMLCs encapsulated in Matrigel plugs migrated to newly grown vasculature, where they produced elastin to stabilize the blood vessels ...
TY - JOUR. T1 - Molecular Criteria for Defining the Naive Human Pluripotent State. AU - Theunissen, Thorold W.. AU - Friedli, Marc. AU - He, Yupeng. AU - Planet, Evarist. AU - ONeil, Ryan C.. AU - Markoulaki, Styliani. AU - Pontis, Julien. AU - Wang, Haoyi. AU - Iouranova, Alexandra. AU - Imbeault, Michaël. AU - Duc, Julien. AU - Cohen, Malkiel A.. AU - Wert, Katherine J.. AU - Castanon, Rosa. AU - Zhang, Zhuzhu. AU - Huang, Yanmei. AU - Nery, Joseph R.. AU - Drotar, Jesse. AU - Lungjangwa, Tenzin. AU - Trono, Didier. AU - Ecker, Joseph R.. AU - Jaenisch, Rudolf. PY - 2016/10/6. Y1 - 2016/10/6. N2 - Recent studies have aimed to convert cultured human pluripotent cells to a naive state, but it remains unclear to what extent the resulting cells recapitulate in vivo naive pluripotency. Here we propose a set of molecular criteria for evaluating the naive human pluripotent state by comparing it to the human embryo. We show that transcription of transposable elements provides a sensitive measure of ...
Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and ...
TY - JOUR. T1 - The polycomb group protein L3MBTL1 repreßes a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells. AU - Perna, Fabiana. AU - Vu, Ly P.. AU - Themeli, Maria. AU - Kriks, Sonja. AU - Hoya-Arias, Ruben. AU - Khanin, Raya. AU - Hricik, Todd. AU - Mansilla-Soto, Jorge. AU - Papapetrou, Eirini P.. AU - Levine, Roß L.. AU - Studer, Lorenz. AU - Sadelain, Michel. AU - Nimer, Stephen D. PY - 2015. Y1 - 2015. N2 - Epigenetic regulation of key transcriptional programs is a critical mechanism that controls hematopoietic development, and, thus, aberrant expression patterns or mutations in epigenetic regulators occur frequently in hematologic malignancies. We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive hematopoietic-specific transcriptional programs by regulating the expression of SMAD5 and impairing its recruitment to target regulatory regions. ...
Val 9 Cell Line. Based on these two properties, pluripotent cell lines reflect the best available tool for research projects in the field of cell therapy and regenerative medicine. Currently, stem cells are one of the most advanced techniques in research, both in Spain and worldwide, given their potential application in the biomedicine field. Pluripotent stem cells are being used for tissue regeneration, cancer research, rare diseases, and development of new drugs.. Recent studies have demonstrated the efficiency of the human pluripotent stem cells (hPSC) as a putative therapy for several diseases. Various clinical trials are actually testing the suitability of hPSC for clinical practice. Some of the diseases which could be treated through cell therapy with hPSC are: Diabetes, Parkinson, macular degeneration, Alzheimer, autism, severe anemia, muscular atrophy, spinal cord damage and cardiac diseases.. Recently, Japanese researchers provided an example of the latest advances with pluripotent ...
Sorry I should have been a little more specific in my email, we do not support embryonic stem cell research. You can learn more about the debate and the issues involved by reading President Bushs statement on this website: http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html This description of embryonic stem cell research was taken from the NIHs website: "Where do stem cells come from? Pluripotent stem cells are isolated from human embryos that are a few days old. Cells from these embryos can be used to create pluripotent stem cell "lines" -cell cultures that can be grown indefinitely in the laboratory. Pluripotent stem cell lines have also been developed from fetal tissue obtained from fetal tissue (older than 8 weeks of development)." "Embryos from which ESCs [embroyonic stem cells] are extracted are destroyed in the process." I am a Christian and believe we should value all life. It is never okay to destroy one human being in an effort to cure another. As President Bush states, ...
Several groups have described induction of ECs and pericytes from hPSC. However, most of the published protocols are based on serum-containing media or require coculture with stromal cell lines.28-32 More recently published protocols on differentiation in defined media required EB formation or forced aggregation in which hPSC are centrifuged to form compact spheroids or spin EBs.33-35 These protocols are efficient (on average 20% to 30% ECs in the differentiated cultures) but are more difficult to adapt for scaling up EC production. In addition, for the spin EB system, hPSC lines usually have to be adapted to single cell, enzymatic passaging in bulk culture from culture as colonies, which can be difficult and time consuming.36 This also might not be convenient if working with the multiple diseased hiPSC lines at the same time. We also noticed rather high line-to-line variation in the spin EB system when using hiPSC (Orlova, unpublished).. The protocol developed here has high line-to-line ...
This protocol describes a method to generate intermediate mesoderm (IM) cells, which can be sorted and induced to further differentiate into various cells of IM-derived lineages. This highly efficient protocol (more than 90% of the IM cells express OSR1) is based on 2D-differentiation of single embryonic stem cell cultures in serum-free medium ...
TY - JOUR. T1 - Gene expression variability as a unifying element of the pluripotency network. AU - Mason, Elizabeth A.. AU - Mar, Jessica C.. AU - Laslett, Andrew L.. AU - Pera, Martin F.. AU - Quackenbush, John. AU - Wolvetang, Ernst. AU - Wells, Christine A.. PY - 2014/8/12. Y1 - 2014/8/12. N2 - Heterogeneity is a hallmark of stem cell populations, in part due to the molecular differences between cells undergoing self-renewal and those poised to differentiate. We examined phenotypic and molecular heterogeneity in pluripotent stem cell populations, using public gene expression data sets. A high degree of concordance was observed between global gene expression variability and the reported heterogeneity of different human pluripotent lines. Network analysis demonstrated that low-variability genes were the most highly connected, suggesting that these are the most stable elements of the gene regulatory network and are under the highest regulatory constraints. Known drivers of pluripotency were ...
Reaping the promise of human embryonic stem (hES) cells hinges on effective defined culture conditions. Efforts to identify chemically defined environments for hES cell propagation would benefit from understanding the relevant functional properties of the substratum. Biological materials are often e …
Photoreceptor loss in retinal degeneration is the major cause of blindness (Hartong et al., 2006; Rattner and Nathans, 2006). Cell transplantation of photoreceptors and/or RPE cells is one of the most promising therapeutic strategies for incurable retinal degenerative diseases (MacLaren and Pearson, 2007; Osakada and Takahashi, 2009). However, the clinical application of cell transplantation is hampered by the fact that cells are often cultured with materials from other animals, such as feeder cells, serum and recombinant proteins, and this poses a risk in terms of adverse immune responses and potential exposure to xenopathogens (Martin et al., 2005). In the present study, we have established a method of inducing retinal differentiation of human ES cells and iPS cells using the chemical compounds CKI-7, SB-431542 and Y-27632. These chemical compounds are non-biological, do not trigger immune responses, have stable activity, show little difference between production lots, and are inexpensive. ...
Intrigued by significant yet insufficient enhancement through the OP9 co-culture in erythroid maturation, we hypothesized that the HE-derived erythroblasts lack the intrinsic ability to reach enucleation, and a specific niche is required at an early stage to prime the HE cells to generate erythroblasts with full maturation potential. The endothelial niche platform of E4EC has been reported to deliver a promoting effect on the generation of engraftable hematopoietic stem and progenitor cells (HSPC) from hPSC.13,14 Considering that HSC emerged from HE cells is in an endothelial microenvironment in AGM, we established a sequential niche system, consisting of endothelial cells (EC) on stage 1 and OP9 on stage 2 (Figure 1A and Figure 2D). After co-culture of D5 HE cells on E4ECs for eight days, the EC-primed erythroblasts (D5+E8) were transferred onto OP9 cells for continuing erythroid maturation. Flow cytometry analysis of band3 and α4 integrin demonstrated that there was a decrease in the α4 ...
Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.
Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.
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STEMCELL Technologies is pleased to introduce STEMdiff™, our new line of products specifically optimized for the differentiation of hPSCs.
Our research is aimed at developing new therapies for patients with severe liver diseases. To restore liver function in patients with liver failure, we are working on generating hepatocytes from human pluripotent stem cells or by reprogramming of readily accessible human cell types. To be therapeutically effective, these cells need to replicate both function and the ability to proliferate of primary human hepatocytes. To establish and improve protocols for the production of such cells, we have been working on obtaining a detailed molecular understanding of hepatocyte differentiation and regeneration. For this, we are using mouse models for liver cell lineage tracing developed in our laboratory. In addition, we are using rigorous animal models of human liver failure to test the therapeutic efficacy of our surrogate hepatocytes. While developing novel liver cell therapies is our main focus, we are also using hepatocytes derived from human pluripotent stem cells or by reprogramming to generate in ...
Ulfenborg B1, Karlsson A2, Riveiro M2, Améen C3, Åkesson K3, Andersson CX3, Sartipy P1,4, Synnergren J1. Abstract The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological ...
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Numerous human disorders of the blood system would directly or indirectly benefit from therapeutic approaches that reconstitute the hematopoietic system. Hemato
Advanced heart failure represents a major unmet clinical need, arising from the loss of viable or fully functional cardiac muscle cells. Despite optimum drug th...
Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying th
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The present invention relates to methods for encapsulating pancreatic progenitors in a biocompatible semi-permeable encapsulating device. The present invention also relates to production of human insulin in a mammal in response to glucose stimulation.
Trevigens Cultrex® stem cell qualified proteins provide a functionally defined and effective feeder-free surface for the attachment and maintenance of embryonic stem cells in a pluripotent state. Our exclusive Human Vitronectin, Human Fibronectin, Mouse Laminin I, and Mouse Reduced Growth Factor Basement Membrane Matrix can support robust, long term proliferation of human embryonic and induced pluripotent stem cells in an undifferentiated state. The matrices can be used to coat tissue culture surfaces and promote cell adhesion and proliferation, or as an additive to cell-culture media. Additionally, we also offer our Cultrex® Embryoid Body (EB) Formation Kit that generates consistent, reproducible and identical in size embryoid bodies (EBs). This kit has been qualified to form EBs from human pluripotent stem cells (hESCs and iPSCs).. ...
Autori: Jerabek S., Merino F., Schöler H.R., Cojocaru V.. Editorial: Elsevier, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, 1839(3), p.138-54, 2014.. Rezumat:. OCT4 was discovered more than two decades ago as a transcription factor specific to early embryonic development. Early studies with OCT4 were descriptive and looked at determining the functional roles of OCT4 in the embryo as well as in pluripotent cell lines derived from embryos. Later studies showed that OCT4 was one of the transcription factors in the four-factor cocktail required for reprogramming somatic cells into induced pluripotent stem cells (iPSCs) and that it is the only factor that cannot be substituted in this process by other members of the same protein family. In recent years, OCT4 has emerged as a master regulator of the induction and maintenance of cellular pluripotency, with crucial roles in the early stages of differentiation. Currently, mechanistic studies look at elucidating the molecular details of ...
It has been widely reported that human pluripotent stem cells (hPSCs) can become karyotypically unstable during their prolonged culture in vitro (1-4). These cytogenetic changes bear stark similarities to those found in many human cancers raising safety concerns for their potential use in regenerative medicine. Although the mechanisms behind these changes are still to be elucidated, they have been shown to provide variant cells with a selective advantage and rapidly out-compete normal cells in culture.. Characteristics of karyotypically abnormal hPSCs include resistance to apoptosis, altered differentiation patterns and persistent stem cells populations in teratomas. As the first clinical trials using hPSC-derived cells are underway, it is imperative that we understand the implications of these changes and how to detect and minimize their occurrence in hPSC cultures.. "Safety of hPSC-derived cellular products is the first and foremost requirement for fulfillment of hPSC clinical potential," says ...