Functional consequences of overexpressing the gap junction Cx43 in the cardiogenic potential of pluripotent human embryonic stem cells

Biochem Biophys Res Commun. 2008 Dec 5;377(1):46-51. doi: 10.1016/j.bbrc.2008.09.076. Epub 2008 Sep 25.

Abstract

Gap junctions, encoded by the connexin (Cx) multi-gene family, couple adjacent cells and underlie cell-cell communications. Previous mouse studies suggest that Cxs play an important role in development but their role in human cardiogenesis is undefined. Human embryonic stem cells (hESC) provide a unique model for studying human differentiation. Lentivirus-mediated stable overexpression of Cx43 in hESC (Cx43-hESC) did not affect colony morphology, karyotype and expression of pluripotency genes such as Oct4 but completely suppressed the formation of spontaneously beating, cardiomyocyte-containing clusters in embryoid bodies (EBs). Unlike control hEBs, the transcripts of several mesodermal markers (kallikrein, delta-globin, and CMP), ventricular myosin light chain and cardiac troponin I were absent or delayed. Transcriptomic and pathway analyses showed that 194 genes crucial for movement, growth, differentiation and maintenance were differentially expressed in Cx43-hESC. We conclude that Cx43 mediates the expression of an array of genes involved in human cardiogenesis, in addition to intercellular communication.

Publication types

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

MeSH terms

  • Animals
  • Cell Communication / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / physiology*
  • Gap Junctions / metabolism*
  • Gene Expression Regulation, Developmental*
  • Heart / embryology*
  • Humans
  • Myocytes, Cardiac / cytology
  • Organogenesis / genetics*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / physiology*
  • Rats
  • Transcription, Genetic

Substances

  • Connexin 43