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Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
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Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes
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What we know about cardiomyocyte dedifferentiation.

Yike Zhu1, Vinh Dang Do1, A Mark Richards2

  • 1Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cardiovascular Disease Translational Research Programme, National University Health Systems, Singapore; Genome Institute of Singapore, Agency of Science Research and Technology, Singapore.

Journal of Molecular and Cellular Cardiology
|December 4, 2020
PubMed
Summary

Cardiomyocyte dedifferentiation, a process where mature heart cells revert to a less mature state, is crucial for heart regeneration. Understanding this plasticity is key to developing new treatments for heart failure.

Keywords:
Cardiomyocyte dedifferentiationCell statesDevelopmentEpigeneticsHeart failure

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Area of Science:

  • Cardiology
  • Developmental Biology
  • Regenerative Medicine

Background:

  • Cardiomyocytes (CMs) have limited regenerative capacity after cardiac injury and heart failure (HF).
  • Promoting CM cell-cycle re-entry is a key strategy for cardiac regeneration.
  • CM dedifferentiation, a reversal to a less mature state, is believed to precede proliferation but remains poorly understood.

Purpose of the Study:

  • To review the current knowledge on cardiomyocyte dedifferentiation in both natural and experimental settings.
  • To explore the phenotypes, molecular mechanisms, and significance of CM dedifferentiation in cardiac regeneration.
  • To discuss the challenges and future directions in studying CM dedifferentiation.

Main Methods:

  • Comprehensive literature review of studies on CM dedifferentiation.
  • Analysis of findings from non-mammalian vertebrates (zebrafish) and mammals.
  • Examination of molecular markers, mechanisms, and functional significance.

Main Results:

  • CM dedifferentiation is essential for CM plasticity and potentially for heart regeneration.
  • The mechanisms and precise nature (dedifferentiation vs. plasticity) of CM transition states require further investigation.
  • Knowledge gaps and technical limitations hinder a full understanding of CM dedifferentiation.

Conclusions:

  • CM dedifferentiation plays a significant role in the heart's potential for regeneration.
  • Further research is crucial to overcome current limitations and harness CM plasticity for treating heart disease.
  • Targeting CM dedifferentiation could offer novel therapeutic strategies for cardiac repair.