FRS2α-mediated FGF signals suppress premature differentiation of cardiac stem cells through regulating autophagy activity

Jue Zhang, Junchen Liu, Yanqing Huang, Julia Y.F. Chang, Leyuan Liu, Wallace L. McKeehan, James F. Martin, Fen Wang

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

RATIONALE: Although the fibroblast growth factor (FGF) signaling axis plays important roles in heart development, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. OBJECTIVE: To investigate the mechanism by which FGF signaling regulates cardiac progenitor cell differentiation. METHODS AND RESULTS: Using mice with tissue-specific ablation of FGF receptors and FGF receptor substrate 2α (Frs2α) in heart progenitor cells, we demonstrate that disruption of FGF signaling leads to premature differentiation of cardiac progenitor cells in mice. Using embryoid body cultures of mouse embryonic stem cells, we reveal that FGF signaling promotes mesoderm differentiation in embryonic stem cells but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, we also report that inhibiting FRS2α-mediated signals increases autophagy and that activating autophagy promotes myocardial differentiation and vice versa. CONCLUSIONS: The results indicate that the FGF/FRS2α-mediated signals prevent premature differentiation of heart progenitor cells through suppressing autophagy. The findings provide the first evidence that autophagy plays a role in heart progenitor differentiation.

Original languageEnglish (US)
Pages (from-to)e29-e39
JournalCirculation Research
Volume110
Issue number4
DOIs
StatePublished - Feb 17 2012

Keywords

  • FGF
  • autophagy
  • heart defect
  • heart development
  • premature differentiation
  • second heart field

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'FRS2α-mediated FGF signals suppress premature differentiation of cardiac stem cells through regulating autophagy activity'. Together they form a unique fingerprint.

Cite this