Chamber-Specific Protein Expression during Direct Cardiac Reprogramming

Forced expression of core cardiogenic transcription factors can directly reprogram fibroblasts to induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. This cardiac reprogramming approach provides a proof of concept for induced heart regeneration by converting a fibroblast fate to a cardiomyocyte fate. However, it remains elusive whether chamber-specific cardiomyocytes can be generated by cardiac reprogramming. Therefore, we assessed the ability of the cardiac reprogramming approach for chamber specification in vitro and in vivo. We found that in vivo cardiac reprogramming post-myocardial infarction exclusively induces a ventricular-like phenotype, while a major fraction of iCMs generated in vitro failed to determine their chamber identities. Our results suggest that in vivo cardiac reprogramming may have an inherent advantage of generating chamber-matched new cardiomyocytes as a potential heart regenerative approach.

Automated summary

Forced expression of core cardiogenic transcription factors can reprogram fibroblasts to induced cardiomyocyte-like cells, showing potential for heart regeneration. However, it is uncertain whether chamber-specific cardiomyocytes can be generated through this approach. In vivo cardiac reprogramming post-myocardial infarction induces a ventricular-like phenotype, while in vitro generated iCMs fail to determine their chamber identities, suggesting a potential advantage of in vivo cardiac reprogramming for chamber-matched new cardiomyocyte generation.