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. Review uri icon

Overview

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.

publication date

  • September 1, 2009

Research

keywords

  • Cell Differentiation
  • Homeodomain Proteins
  • MicroRNAs
  • Octamer Transcription Factor-3
  • Pluripotent Stem Cells
  • SOXB1 Transcription Factors
  • Transcription, Genetic

Identity

PubMed Central ID

  • PMC3135180

Scopus Document Identifier

  • 67650810301

Digital Object Identifier (DOI)

  • 10.1089/scd.2009.0113

PubMed ID

  • 19480567

Additional Document Info

volume

  • 18

issue

  • 7