Reprogramming of cardiac cell fate as a therapeutic strategy for ischemic heart disease

J Mol Cell Cardiol. 2023 Jun:179:2-6. doi: 10.1016/j.yjmcc.2023.03.013. Epub 2023 Mar 29.

Abstract

Direct reprogramming of resident cardiac fibroblasts to induced cardiomyocytes is an attractive therapeutic strategy to restore function and remuscularize the injured heart. The cardiac transcription factors Gata4, Mef2c, and Tbx5 have been the mainstay of direct cardiac reprogramming strategies for the past decade. Yet, recent discoveries have identified alternative epigenetic factors capable of reprogramming human cells in the absence of these canonical factors. Further, single-cell genomics evaluating cellular maturation and epigenetics in the setting of injury and heart failure models following reprogramming have continued to inform the mechanistic underpinnings of this process and point toward future areas of discovery for the field. These discoveries and others covered in this review have provided complementary approaches that further enhance the effectiveness of reprogramming as a means of promoting cardiac regeneration following myocardial infarction and heart failure.

Keywords: Cardiac regeneration; Cardiac reprogramming; Epigenetics; Heart failure.

Publication types

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

MeSH terms

  • Cell Differentiation
  • Cellular Reprogramming / genetics
  • Fibroblasts
  • Heart Failure* / genetics
  • Heart Failure* / therapy
  • Humans
  • Myocardial Infarction* / therapy
  • Myocytes, Cardiac