Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal

Kathy K. Niakan, Hongkai Ji, René Maehr, Steven A. Vokes, Kit T. Rodolfa, Richard I. Sherwood, Mariko Yamaki, John T. Dimos, Alice E. Chen, Douglas A. Melton, Andrew P. McMahon, Kevin Eggan

Research output: Contribution to journalArticle

Abstract

In embryonic stem (ES) cells, a well-characterized transcriptional network promotes pluripotency and represses gene expression required for differentiation. In comparison, the transcriptional networks that promote differentiation of ES cells and the blastocyst inner cell mass are poorly understood. Here, we show that Sox17 is a transcriptional regulator of differentiation in these pluripotent cells. ES cells deficient in Sox17 fail to differentiate into extraembryonic cell types and maintain expression of pluripotency-associated transcription factors, including Oct4, Nanog, and Sox2. In contrast, forced expression of Sox17 down-regulates ES cellassociated gene expression and directly activates genes functioning in differentiation toward an extraembryonic endoderm cell fate.We show these effects of Sox17 on ES cell gene expression are mediated at least in part through a competition between Sox17 and Nanog for common DNA-binding sites. By elaborating the function of Sox17, our results provide insight into how the transcriptional network promoting ES cell self-renewal is interrupted, allowing cellular differentiation.

Original languageEnglish (US)
Pages (from-to)312-326
Number of pages15
JournalGenes and Development
Volume24
Issue number3
DOIs
StatePublished - Feb 1 2010

Keywords

  • Differentiation
  • Primitive endoderm
  • Self-renewal
  • Sox17
  • Stem cell
  • Transcriptional network

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Niakan, K. K., Ji, H., Maehr, R., Vokes, S. A., Rodolfa, K. T., Sherwood, R. I., Yamaki, M., Dimos, J. T., Chen, A. E., Melton, D. A., McMahon, A. P., & Eggan, K. (2010). Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal. Genes and Development, 24(3), 312-326. https://doi.org/10.1101/gad.1833510