Caspase activity mediates the differentiation of embryonic stem cells

Cell Stem Cell. 2008 Jun 5;2(6):595-601. doi: 10.1016/j.stem.2008.04.001.


Embryonic stem cells (ESCs) are capable of indefinite self-renewal while retaining the ability to differentiate to any of the three germ layers that give rise to all somatic cell types. An emerging view is that a core set of transcription factors, including Oct4, Sox2, and Nanog, form a robust autoregulatory circuit that maintains ESCs in a self-renewing state. To accommodate the capacity of such cells to undergo germ layer-specific differentiation, we predicted a posttranslational mechanism that could negatively regulate these core self-renewal factors. Here we report caspase-induced cleavage of Nanog in differentiating ESCs. Stem cells lacking the Casp3 gene showed marked defects in differentiation, while forced expression of a caspase cleavage-resistant Nanog mutant in ESCs strongly promoted self-renewal. These results link a major component of the programmed cell-death pathway to the regulation of ESC development.

Publication types

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

MeSH terms

  • Animals
  • Caspase 3 / genetics*
  • Caspase 3 / metabolism*
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Line
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / enzymology*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mutagenesis, Site-Directed
  • Nanog Homeobox Protein
  • Transcriptional Activation
  • Transfection
  • Transgenes / genetics


  • Homeodomain Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Caspase 3