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Area of Science:

  • Regenerative Medicine
  • Cardiovascular Biology
  • Cell Biology

Background:

  • Fibroblast reprogramming holds promise for myocardial regeneration.
  • Endothelial cell plasticity can potentially enhance reprogramming efficiency.

Purpose of the Study:

  • To explore a novel strategy for enhancing fibroblast reprogramming into cardiomyocytes.
  • To investigate the role of endothelial cell plasticity in cardiac cell transdifferentiation.

Main Methods:

  • Cardiac endothelial cells and fibroblasts were treated with Gata4, Mef2c, and Tbx5 (GMT).
  • Fibroblasts were treated with ETV2 to induce an endothelial cell state before GMT treatment.
  • Cardiomyocyte marker expression (cTnT) and functional assays (calcium transients, contractility) were assessed.

Main Results:

  • Endothelial cells treated with GMT yielded more cTnT+ cells than cardiac fibroblasts.
  • Fibroblasts treated with ETV2 followed by GMT showed significantly higher cTnT expression than GMT or ETV2 alone.
  • GMT+ETV2 treated fibroblasts exhibited calcium transients and synchronous contractility in co-culture.

Conclusions:

  • Transiently inducing an endothelial cell state enhances fibroblast reprogramming into cardiomyocytes.
  • Cardiac fibroblast transdifferentiation via an endothelial intermediate improves plasticity and cardio-differentiation efficiency.
  • This
  • trans-endothelial
  • approach offers a promising strategy for myocardial regeneration.