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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

Kashyap, Vasundhra; Rezende, Naira C.; Scotland, Kymora B.; Shaffer, Sebastian M.; Persson, Jenny L LU ; Gudas, Lorraine J. and Mongan, Nigel P. (2009) In Stem Cells and Development 18(7). p.1093-1108
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Stem Cells and Development
volume
18
issue
7
pages
1093 - 1108
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000269701000014
  • scopus:67650810301
ISSN
1557-8534
DOI
10.1089/scd.2009.0113
language
English
LU publication?
yes
id
31899f62-0460-4cba-9fb3-a2a15f1ee9ab (old id 1490860)
date added to LUP
2009-10-19 11:06:30
date last changed
2017-11-19 03:30:33
@article{31899f62-0460-4cba-9fb3-a2a15f1ee9ab,
  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.},
  author       = {Kashyap, Vasundhra and Rezende, Naira C. and Scotland, Kymora B. and Shaffer, Sebastian M. and Persson, Jenny L and Gudas, Lorraine J. and Mongan, Nigel P.},
  issn         = {1557-8534},
  language     = {eng},
  number       = {7},
  pages        = {1093--1108},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Stem Cells and Development},
  title        = {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},
  url          = {http://dx.doi.org/10.1089/scd.2009.0113},
  volume       = {18},
  year         = {2009},
}