Control of cell fate upon transcription factor-driven cardiac reprogramming.

Curr Opin Genet Dev

The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Published: December 2024

AI Article Synopsis

  • Adult mammals experience significant loss of heart cells (cardiomyocytes) after heart diseases, largely because these cells have a limited ability to grow back.
  • Researchers have recently developed methods to convert fibroblasts (a type of cell) into new cardiomyocytes using specific proteins called transcription factors, both in lab conditions and within living organisms.
  • The review highlights improvements in the processes used for this cell transformation, discusses new insights from advanced single-cell studies, and addresses the current challenges and future directions in the field of cardiac reprogramming.

Article Abstract

Adult mammals are susceptible to substantial cardiomyocyte (CM) loss following various cardiac diseases due to the limited capacity of CM proliferation and regeneration. Recently, direct cardiac reprogramming, converting fibroblasts into induced CMs, has been achieved both in vitro and in vivo through forced expression of transcription factors (TFs). This review encapsulates the advancements made in enhancing reprogramming efficiency and underlying molecular mechanisms. It covers the optimization of TF-based reprogramming cocktails and in vivo delivery platform and recently identified regulators in enhancing reprogramming efficiency. In addition, we discuss recent insights into the molecular mechanisms of direct cardiac reprogramming from single-cell omics analyses. Finally, we briefly touch on remaining challenges and prospective direction of this field.

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http://dx.doi.org/10.1016/j.gde.2024.102226DOI Listing

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