Discovering the mechanism behind cardiomyocyte maturation

An RNA splicing regulator has been shown to promote cardiomyocyte maturation, offering hope for novel cardiac regenerative therapies.

The maturation of cardiomyocytes from the neonatal to the adult stages involves significant changes to the structure and functionality of the cells. The mechanism behind this process remains a mystery that researchers are still trying to unravel.

In the latest developments, a team of researchers from the University of California, Los Angeles (CA, US) and Duke-NUS Medical School (Singapore) have identified an internal control mechanism that promotes the development of cardiomyocytes from their immature fetal stage to their mature adult form. The findings could pave the way for novel cardiac regenerative therapies for heart disease and damage. 

Utilizing a pre-clinical model, the researchers noticed an increase in the expression of an RNA splicing regulator known as Rbfox1 in adult cardiomyocytes compared to neonatal cardiomyocytes. The increased expression levels of the regulator during cardiomyocyte maturation were further confirmed by single-cell RNA sequencing data from previously published studies, suggesting that RNA splicing control may play a significant role in postnatal cardiomyocyte maturation. 

“While RBFox1 alone may not be sufficient to push mature fetal heart muscle cells all the way to fully matured adult cells, our findings uncover a new RNA-based internal network that can substantially drive this maturation process beyond other available approaches,” commented Jijun Huang, lead author of the study.  

Senior author of the study, Yibin Wang, said, “These findings present a potential molecular approach to enhance heart cell maturation, which could address a major challenge in the domains of cardiac regenerative therapy and disease modeling.” 

The study marks one of the first to show altering RNA splicing could encourage significant maturation of cardiomyocytes derived from human stem cells. 

While further research is required to expand upon the findings from the initial study, the prospect of reshaping cardiac care through the development of novel cardiac regenerative therapies is on the horizon.