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Sox2 acts through Sox21 to regulate transcription in pluripotent and differentiated cells

Andrey N Kuzmichev1, Suel-Kee Kim, Ana C D'Alessio

  • 1Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

Current Biology : CB
|August 21, 2012
PubMed

Insights

Sox2 (Sex-determining region Y-box 2) rapidly induces Sox21, a key factor in regulating cell identity. This mechanism impacts stem cell renewal, differentiation, and reprogramming across various cell types, including in colon cancer.

Area of Science:

  • Stem cell biology
  • Transcriptional regulation
  • Cancer research

Background:

  • Sox2 is a crucial transcriptional regulator in stem cells and an oncogene in endodermal cancers.
  • Understanding Sox2's cooperative transcriptional action is vital for stem cell renewal, differentiation, and reprogramming.
  • A general understanding of Sox2's transcriptional mechanisms is currently lacking.

Purpose of the Study:

  • To identify transcriptional partners of Sox2 in adult cells.
  • To elucidate the role of Sox2 in intestinal stem cell regulation.
  • To investigate the mechanism by which Sox2 influences cell identity.

Main Methods:

  • Generation of inducible mouse models for studying Sox2 gene expression.
  • In vivo analysis of Sox2 effects in the rapidly self-renewing intestinal epithelium.
  • In vitro experiments using colon cancer cells and pluripotent stem cells.

Main Results:

  • Sox2 expression increased intestinal stem cell numbers and repressed Cdx2, a key regulator of endodermal identity.
  • Sox21 was identified as a specific, immediate, and cell-autonomous target of Sox2 in intestinal stem cells.
  • Sox21 repressed Cdx2 in colon cancer and pluripotent stem cells, and its induction by Sox2 in fibroblasts was necessary for reprogramming.

Conclusions:

  • Transcriptional induction of Sox21 is a rapid and general mediator of Sox2's effects on cell identity.
  • Sox2 influences cell fate through the induction of Sox21 in diverse cell types.
  • This study reveals a novel mechanism for Sox2-mediated regulation of cell identity and reprogramming.

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