OSKM-mediated reversible reprogramming of cardiomyocytes regenerates injured myocardium

Gregory Farber,Jiandong Liu,Li Qian

doi:10.1186/s13619-021-00106-3

Gregory Farber, Jiandong Liu + Show 1 more

Open Access

https://doi.org/10.1186/s13619-021-00106-3

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Abstract

Cellular reprogramming has rapidly become a promising methodology to generate new cardiomyocytes from non-cardiomyocyte cell types. Using the transient expression of OSKM factors, Chen et al. demonstrate a unique reprogramming strategy involving the modulation of the resident adult cardiomyocyte identity to an immature proliferative state (Science 373:1537–40, 2021). This OSKM-mediated reversion results in the adoption by adult murine cardiomyocytes of a transcriptional profile similar to cardiomyocytes found in developing hearts, as well as increased proliferative capacity of these reprogrammed cardiomyocytes compared to mature cardiomyocytes. Furthermore, this novel approach enhances the regeneration of adult murine hearts post-myocardial injury. Although concerns and questions remain, the encouraging results of this study advance the field of cardiac regeneration by providing a new technique to generate cardiomyocytes as well as insights into cardiomyocyte dedifferentiation and its relation to proliferation.

Highlights

The high global prevalence of cardiac injury and disease has made finding new sources for cardiomyocytes an ever-evolving area of research
While other reprogramming strategies seek to create mature cardiomyocytes to replace damaged ones, this study seeks to obtain an earlier stage of cardiomyocyte identity which may result in increased proliferation potential at the expense of losing key functional attributes
Other groups have evaluated proteins involved in the Hippo pathway as well as transcription factors like Gata4 and Meis1 (Mahmoud et al, 2013; Malek Mohammadi et al, 2017). All of these approaches have shown varying degrees of promise in allowing cardiomyocytes to enter a more proliferative state, they may benefit from application of knowledge obtained from OSKM-mediated reversible reprogramming in order to further hone in on specific pathways

Summary

Introduction

The high global prevalence of cardiac injury and disease has made finding new sources for cardiomyocytes an ever-evolving area of research. Direct and indirect (via iPSC route) reprogrammingbased methods are attractive options for generating new cardiomyocytes from non-cardiomyocyte cell types and have shown promise as potential therapeutic tools for heart regeneration (Ieda et al 2010; Qian et al 2012; Shiba et al 2016; Song et al 2012; Wang et al 2021).

Results

Conclusion