Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells

Shinji Masui, Yuhki Nakatake, Yayoi Toyooka, Daisuke Shimosato, Rika Yagi, Kazue Takahashi, Hitoshi Okochi, Akihiko Okuda, Ryo Matoba, Alexei A. Sharov, Minoru S.H. Ko, Hitoshi Niwa

Research output: Contribution to journalArticle

789 Citations (Scopus)

Abstract

The pluripotency of embryonic stem (ES) cells is thought to be maintained by a few key transcription factors, including Oct3/4 and Sox2. The function of Oct3/4 in ES cells has been extensively characterized, but that of Sox2 has yet to be determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cell-specific genes, including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct-Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating multiple transcription factors that affect Oct3/4 expression and that the forced expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.

Original languageEnglish
Pages (from-to)625-635
Number of pages11
JournalNature Cell Biology
Volume9
Issue number6
DOIs
Publication statusPublished - 2007 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    Masui, S., Nakatake, Y., Toyooka, Y., Shimosato, D., Yagi, R., Takahashi, K., Okochi, H., Okuda, A., Matoba, R., Sharov, A. A., Ko, M. S. H., & Niwa, H. (2007). Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nature Cell Biology, 9(6), 625-635. https://doi.org/10.1038/ncb1589