SOX9 accelerates ESC differentiation to three germ layer lineages by repressing SOX2 expression through P21 (WAF1/CIP1)

Kohei Yamamizu, David Schlessinger, Minoru Ko

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Upon removal of culture conditions that maintain an undifferentiated state, mouse embryonic stem cells (ESCs) differentiate into various cell types. Differentiation can be facilitated by forced expression of certain transcription factors (TFs), each of which can generally specify a particular developmental lineage. We previously established 137 mouseESClines, each of which carried a doxycycline-controllable TF. Among them, Sox9 has unique capacity: its forced expression accelerates differentiation of mouse ESCs into cells of all three germ layers. With the additional use of specific culture conditions, overexpression of Sox9 facilitated the generation of endothelial cells, hepatocytes and neurons from ESCs. Furthermore, Sox9 action increases formation of p21 (WAF1/CIP1), which then binds to the SRR2 enhancer of pluripotency marker Sox2 and inhibits its expression. Knockdown of p21 abolishes inhibition of Sox2 and Sox9-accelerated differentiation, and reduction of Sox2 2 days after the beginning of ESC differentiation can comparably accelerate mouse ESC formation of cells of three germ layers. These data implicate the involvement of the p21-Sox2 pathway in the mechanism of accelerated ESC differentiation by Sox9 overexpression. The molecular cascade could be among the first steps to program ESC differentiation.

Original languageEnglish
Pages (from-to)4254-4266
Number of pages13
JournalDevelopment (Cambridge)
Volume141
Issue number22
DOIs
Publication statusPublished - 2014 Nov 1

Fingerprint

Germ Layers
Embryonic Stem Cells
Cell Differentiation
Transcription Factors
Doxycycline
Hepatocytes
Endothelial Cells
Neurons
Mouse Embryonic Stem Cells

Keywords

  • Cdkn1a (P21/WAF1/CIP1)
  • Embryonic stem cells
  • Sox2
  • Sox9

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Medicine(all)

Cite this

SOX9 accelerates ESC differentiation to three germ layer lineages by repressing SOX2 expression through P21 (WAF1/CIP1). / Yamamizu, Kohei; Schlessinger, David; Ko, Minoru.

In: Development (Cambridge), Vol. 141, No. 22, 01.11.2014, p. 4254-4266.

Research output: Contribution to journalArticle

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