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RNA-binding protein SAMD4A targets FGF2 to regulate cardiomyocyte lineage specification from human embryonic stem

Na Yi1,2,3, Han-Rui Wang1,2,3, Yu-Ping Zhu1,2,3

  • 1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.

Stem Cell Research & Therapy
|March 19, 2025
PubMed

Insights

SAMD4A, an RNA-binding protein, is crucial for heart development. It regulates cardiomyocyte lineage commitment by controlling FGF2 expression and AKT signaling, offering insights into congenital heart disease therapies.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Biology
  • Molecular Mechanisms of Development

Background:

  • RNA-binding proteins (RBPs) play vital roles in cardiac development.
  • Many RBPs involved in heart development remain uncharacterized.

Purpose of the Study:

  • To investigate the role of SAMD4A in cardiomyocyte lineage specification.
  • To elucidate the molecular mechanisms by which SAMD4A influences cardiac development.

Main Methods:

  • Utilized a human embryonic stem cell (hESC) differentiation model into cardiomyocytes.
  • Generated SAMD4A-knockdown and SAMD4A-overexpressing hESC lines.

Main Results:

  • SAMD4A expression increases during early heart development.
  • SAMD4A suppression impairs hESC proliferation, cardiac mesoderm differentiation, and cardiomyocyte function.
  • SAMD4A binds FGF2 mRNA, stabilizing it and enhancing translation, thus upregulating FGF2 and modulating AKT signaling.
  • FGF2 supplementation rescues proliferation defects caused by SAMD4A absence.

Conclusions:

  • SAMD4A is essential for cardiomyocyte lineage commitment via post-transcriptional regulation of FGF2 and AKT signaling modulation.
  • This study highlights SAMD4A's role in cardiac organogenesis.
  • Findings provide insights into heart development mechanisms and potential therapeutic strategies for congenital heart disease.
Abstract

Keywords:
Cardiomyocyte differentiationFGF2FGFR2RNA-binding proteinSAMD4AStem cell

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