Talk:Stem Cells - Induced: Difference between revisions
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==2009== | ==2009== | ||
===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=== | ===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=== |
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Cite this page: Hill, M.A. (2024, June 2) Embryology Stem Cells - Induced. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Stem_Cells_-_Induced |
2009
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