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. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Kashyap V, Rezende NC, Scotland KB, Shaffer SM, Persson JLiao, Gudas LJ, Mongan NP |
Journal | Stem Cells Dev |
Volume | 18 |
Issue | 7 |
Pagination | 1093-108 |
Date Published | 2009 Sep |
ISSN | 1557-8534 |
Keywords | Animals, Cell Differentiation, Cell Transformation, Neoplastic, DNA Methylation, Epigenesis, Genetic, Homeodomain Proteins, Humans, MicroRNAs, Nanog Homeobox Protein, Neoplastic Stem Cells, Octamer Transcription Factor-3, Pluripotent Stem Cells, SOXB1 Transcription Factors, Transcription, Genetic |
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. |
DOI | 10.1089/scd.2009.0113 |
Alternate Journal | Stem Cells Dev. |
PubMed ID | 19480567 |
PubMed Central ID | PMC3135180 |
Grant List | T32 MH018882-20 / MH / NIMH NIH HHS / United States F31CA123703-02 / CA / NCI NIH HHS / United States R01CA043786 / CA / NCI NIH HHS / United States T32 MH018882 / MH / NIMH NIH HHS / United States UL1RR024996 / RR / NCRR NIH HHS / United States T32MH018882 / MH / NIMH NIH HHS / United States F31 CA123703-02 / CA / NCI NIH HHS / United States R01CA097543 / CA / NCI NIH HHS / United States R01 CA043796 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States R01 DE010389 / DE / NIDCR NIH HHS / United States R01 CA097543 / CA / NCI NIH HHS / United States |