Rho-Signaling-Directed YAP/TAZ Activity Underlies the Long-Term Survival and Expansion of Human Embryonic Stem Cells

Cell Stem Cell. 2015 Oct 1;17(4):448-61. doi: 10.1016/j.stem.2015.07.009. Epub 2015 Aug 27.

Abstract

Human embryonic stem cells (hESCs) can survive and proliferate for an extended period of time in culture, but unlike that of tumor-derived cells, this form of cellular immortality does not depend on genomic aberrations. In this study, we sought to elucidate the molecular basis of this long-term growth property of hESCs. We found that the survival of hESCs depends on the small GTPase Rho and its activator AKAP-Lbc. We show that AKAP-Lbc/Rho signaling sustains the nuclear function of the transcriptional cofactors YAP and TAZ by modulating actin microfilament organization. By inducing reprogramming and differentiation, we found that dependency on this Rho signaling pathway is associated with the pluripotent state. Thus, our findings show that the capacity of hESCs to undergo long-term expansion in vitro is intrinsically coupled to their cellular identity through interconnected molecular circuits that link cell survival to pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins / metabolism*
  • Actin Cytoskeleton
  • Actin Depolymerizing Factors / metabolism*
  • Cell Cycle Proteins
  • Cell Proliferation
  • Cell Self Renewal
  • Cell Survival
  • Cells, Cultured
  • Human Embryonic Stem Cells / cytology
  • Human Embryonic Stem Cells / metabolism*
  • Humans
  • Nuclear Proteins / metabolism*
  • Transcription Factors / metabolism*
  • rho GTP-Binding Proteins / metabolism*

Substances

  • A Kinase Anchor Proteins
  • Actin Depolymerizing Factors
  • Cell Cycle Proteins
  • Nuclear Proteins
  • TAZ protein, human
  • Transcription Factors
  • YY1AP1 protein, human
  • rho GTP-Binding Proteins

Associated data

  • GEO/GSE67128