Context-dependent wiring of Sox2 regulatory networks for self-renewal of embryonic and trophoblast stem cells

Mol Cell. 2013 Nov 7;52(3):380-92. doi: 10.1016/j.molcel.2013.09.002. Epub 2013 Oct 10.


Sox2 is a transcription factor required for the maintenance of pluripotency. It also plays an essential role in different types of multipotent stem cells, raising the possibility that Sox2 governs the common stemness phenotype. Here we show that Sox2 is a critical downstream target of fibroblast growth factor (FGF) signaling, which mediates self-renewal of trophoblast stem cells (TSCs). Sustained expression of Sox2 together with Esrrb or Tfap2c can replace FGF dependency. By comparing genome-wide binding sites of Sox2 in embryonic stem cells (ESCs) and TSCs combined with inducible knockout systems, we found that, despite the common role in safeguarding the stem cell state, Sox2 regulates distinct sets of genes with unique functions in these two different yet developmentally related types of stem cells. Our findings provide insights into the functional versatility of transcription factors during embryogenesis, during which they can be recursively utilized in a variable manner within discrete network structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Line
  • Embryonic Development / genetics
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • SOXB1 Transcription Factors / immunology
  • SOXB1 Transcription Factors / metabolism*
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factor AP-2 / metabolism
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*


  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Tfap2c protein, mouse
  • Transcription Factor AP-2
  • Fibroblast Growth Factors

Associated data

  • GEO/GSE28455