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Updated: Jan 7, 2026

Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived Cell Migration
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Invasion of Epicardial-Derived Cells to the Trabeculae Mediated by NFPs-Fgf Signaling Regulates Ventricular

Anika Nusrat1, Luqi Zhao1, Lianjie Miao1

  • 1Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy (A.N., L.Z., L.M., M.A.H., M.W.), University of Houston, TX.

Circulation. Heart Failure
|January 1, 2026
PubMed

Insights

Numb family proteins in epicardial cells are crucial for heart development, preventing left ventricular noncompaction cardiomyopathy (LVNC). Restoring FGF signaling partially rescues these developmental defects, highlighting a key pathway in cardiac compaction.

Area of Science:

  • Cardiology
  • Developmental Biology
  • Genetics

Background:

  • Left ventricular noncompaction cardiomyopathy (LVNC) is a significant pediatric heart condition characterized by excessive trabeculation and deep recesses.
  • The precise pathogenesis of LVNC remains incompletely understood, necessitating further investigation into its underlying molecular mechanisms.

Purpose of the Study:

  • To investigate the role of Numb family proteins (NFPs) in epicardial cells (EpiCs) and their contribution to the development of LVNC.
  • To elucidate the molecular pathways, including the FGF/FGFR axis, involved in NFP-mediated cardiac development and compaction.

Main Methods:

  • Utilized a mouse model with epicardium-specific knockout of Numb and Numblike genes (EDKO).
  • Employed lineage tracing to monitor epicardial-derived cell (EPDC) invasion and differentiation.
  • Conducted single-nuclei mRNA sequencing and pharmacological interventions to identify disrupted pathways and potential rescue strategies.

Main Results:

  • Epicardial NFP ablation led to abnormal EPDC differentiation and migration, resulting in LVNC.
  • Single-nuclei sequencing revealed dysregulation of the FGF/FGFR signaling pathway in EDKO hearts.
  • Exogenous FGF2 supplementation partially rescued epithelial-mesenchymal transition and cardiac compaction defects.

Conclusions:

  • Epicardial NFPs are essential for regulating EPDC invasion, differentiation, and cardiomyocyte communication, thereby preventing LVNC.
  • The epicardial NFPs-FGF/FGFR axis plays a critical role in ventricular compaction during heart development.
  • Targeting this axis offers potential therapeutic strategies for LVNC and related cardiac developmental disorders.
Abstract

Keywords:
cardiomyopathiesepicardiumepithelial-mesenchymal transitionfibroblast growth factorfibroblasts

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