Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells

Cell Stem Cell. 2009 Apr 3;4(4):359-69. doi: 10.1016/j.stem.2009.03.001.


Recent evidence indicates that mouse and human embryonic stem cells (ESCs) are fixed at different developmental stages, with the former positioned earlier. We show that a narrow concentration of the naturally occurring short-chain fatty acid, sodium butyrate, supports the extensive self-renewal of mouse and human ESCs, while promoting their convergence toward an intermediate stem cell state. In response to butyrate, human ESCs regress to an earlier developmental stage characterized by a gene expression profile resembling that of mouse ESCs, preventing precocious Xist expression while retaining the ability to form complex teratomas in vivo. Other histone deacetylase inhibitors (HDACi) also support human ESC self-renewal. Our results indicate that HDACi can promote ESC self-renewal across species, and demonstrate that ESCs can toggle between alternative states in response to environmental factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyrates / pharmacology*
  • Cell Differentiation*
  • Embryonic Stem Cells / drug effects*
  • Embryonic Stem Cells / enzymology
  • Embryonic Stem Cells / physiology*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Profiling
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Humans
  • Mice
  • RNA, Long Noncoding
  • RNA, Untranslated / metabolism


  • Butyrates
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • RNA, Long Noncoding
  • RNA, Untranslated
  • XIST non-coding RNA
  • Histone Deacetylases

Associated data

  • GEO/GSE15112