Talk:Stem Cells - Induced
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Cite this page: Hill, M.A. (2026, October 2) Embryology Stem Cells - Induced. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Stem_Cells_-_Induced |
2009
Interplay of Oct4 with Sox2 and Sox17: a molecular switch from stem cell pluripotency to specifying a cardiac fate
J Cell Biol. 2009 Sep 7;186(5):665-73.
Stefanovic S, Abboud N, Désilets S, Nury D, Cowan C, Pucéat M. Source Institut National de la Santé et de la Recherche Médicale (INSERM), Avenir Team, Stem Cells and Cardiogenesis, Evry 91058, France.
Abstract
Oct4 exerts a dose-dependent dual action, as both a gatekeeper for stem cell pluripotency and in driving cells toward specific lineages. Here, we identify the molecular mechanism underlying this dual function. BMP2- or transgene-induced Oct4 up-regulation drives human embryonic and induced pluripotent stem cells to become cardiac progenitors. When embryonic stem cell pluripotency is achieved, Oct4 switches from the Sox2 to the Sox17 promoter. This switch allows the cells to turn off the pluripotency Oct4-Sox2 loop and to turn on the Sox17 promoter. This powerful process generates a subset of endoderm-expressing Sox17 and Hex, both regulators of paracrine signals for cardiogenesis (i.e., Wnt, BMP2) released into the medium surrounding colonies of embryonic stem cells. Our data thus reveal a novel molecular Oct4- and Sox17-mediated mechanism that disrupts the stem cell microenvironment favoring pluripotency to provide a novel paracrine endodermal environment in which cell lineage is determined and commits the cells to a cardiogenic fate.
PMID: 19736317 http://www.ncbi.nlm.nih.gov/pubmed/19736317?
http://jcb.rupress.org/content/186/5/665.full?sid=83d70658-9c78-40a1-a865-908901029de8
Direct cell reprogramming is a stochastic process amenable to acceleration
Nature. 2009 Dec 3;462(7273):595-601. Epub 2009 Nov 8.
Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R. Source The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. Hanna@wi.mit.edu
Abstract
Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency.
PMID: 19898493 http://www.ncbi.nlm.nih.gov/pubmed/19898493
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789972
Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs
Stem Cells Dev. 2009 Sep;18(7):1093-108.
Kashyap V, Rezende NC, Scotland KB, Shaffer SM, Persson JL, Gudas LJ, Mongan NP. Source Department of Pharmacology, Graduate Programs in Pharmacology, Weill Cornell Medical College, New York, New York 10065, USA.
Abstract
Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce transcriptional noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies.
PMID: 19480567 http://www.ncbi.nlm.nih.gov/pubmed/19480567
http://www.liebertonline.com/doi/abs/10.1089/scd.2009.0113 PDF
2008
Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors
Nature. 2008 Jul 31;454(7204):646-50. Epub 2008 Jun 29.
Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Araúzo-Bravo MJ, Ruau D, Han DW, Zenke M, Schöler HR. Source Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, NRW, Germany.
Abstract
Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc and Klf4 (refs 1-11). Considering that ectopic expression of c-Myc causes tumorigenicity in offspring and that retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells. These two-factor iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimaeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.
PMID: 18594515
2004
Characterization of stage-specific embryonic antigen-1 expression during early stages of human embryogenesis
Oncol Rep. 2004 Dec;12(6):1251-6.
Liu S, Liu H, Tang S, Pan Y, Ji K, Ning H, Wang S, Qi Z, Li L. Source Department of Histology and Embryology, Second Military Medical University, Shanghai 200433, PR China.
Abstract
Extensive expression of stage-specific embryonic antigen-1 (SSEA-1) has been documented in some animal species, but not in human embryos. In this study, SSEA-1 was detected during human embryogenesis by whole-mount immunohistochemistry. Alkaline phosphatase (Ap) activity was detected to identify human primordial germ cells. SSEA-1 was expressed steadily and restrictedly in some cells/tissues, especially in the nephric duct and nephric tubule (including the pronephric duct and tubule, mesonephric duct and tubule, metanephric tissues) besides embryonic ectodermal cells and yolk sac from 3 to 7 weeks. High level of Ap activity was observed in vessels, part of the mesonephric duct, especially in embryonic primordial germ cells localized in the yolk sac, primitive gut, dorsal mesenteries and genital ridges. No colocalization of AP and SSEA-1 cells was observed. SSEA-1 was expressed in human embryos in a different pattern at early stages compared to that in mouse embryos. It was expressed in the nephric duct, nephric tubule, yolk sac and on the surface of embryonic ectodermal cells of the epidermis, but not in human primordial germ cells.
PMID: 15547746 http://www.ncbi.nlm.nih.gov/pubmed/15547746
