Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules

Proc Natl Acad Sci U S A. 2010 May 4;107(18):8129-34. doi: 10.1073/pnas.1002024107. Epub 2010 Apr 20.


Using a high-throughput chemical screen, we identified two small molecules that enhance the survival of human embryonic stem cells (hESCs). By characterizing their mechanisms of action, we discovered an essential role of E-cadherin signaling for ESC survival. Specifically, we showed that the primary cause of hESC death following enzymatic dissociation comes from an irreparable disruption of E-cadherin signaling, which then leads to a fatal perturbation of integrin signaling. Furthermore, we found that stability of E-cadherin and the resulting survival of ESCs were controlled by specific growth factor signaling. Finally, we generated mESC-like hESCs by culturing them in mESC conditions. And these converted hESCs rely more on E-cadherin signaling and significantly less on integrin signaling. Our data suggest that differential usage of cell adhesion systems by ESCs to maintain self-renewal may explain their profound differences in terms of morphology, growth factor requirement, and sensitivity to enzymatic cell dissociation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Cell Adhesion
  • Cell Communication
  • Cell Shape
  • Cell Survival
  • Cells, Cultured
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Extracellular Matrix / metabolism
  • Humans
  • Integrins / metabolism
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Signal Transduction*
  • rho GTP-Binding Proteins / metabolism
  • rho-Associated Kinases / metabolism


  • Cadherins
  • Integrins
  • rho-Associated Kinases
  • rho GTP-Binding Proteins