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Cited4a limits CM dedifferentiation and proliferation during zebrafish heart regeneration [Bulk RNA-seq]

ABSTRACT: Cardiac regeneration involves interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been under intense study. Here we report single nuclear RNA sequencing profile of the injured zebrafish heart and identified distinct cardiomyocyte populations in the injured heart. These cardiomyocyte populations indicate diverse functions that includes stress-response, myofibril assembly, proliferation and contraction. The contracting cardiomyocyte population also involves activation of maturation pathways as an early response to injury. This intriguing finding suggests that constant maintenance of distinctive terminally differentiated cardiomyocyte population is important for cardiac function during regeneration. To test this, we determined that cited4a, a p300/CBP transcriptional co-activator, is induced after injury in mature cardiomyocyte population. Moreover, loss-of-cited4a mutants showed increased dedifferentiation, proliferation and accelerated heart regeneration. Thus, suppressing cardiomyocyte maturation pathway activity in injured hearts could be an approach to promote heart regeneration.

ORGANISM(S): Danio rerio

PROVIDER: GSE279843 | GEO | 2025/01/31

REPOSITORIES: GEO

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cited4a limits CM dedifferentiation and proliferation during zebrafish heart regeneration [snRNA-seq]

Project description:Cardiac regeneration involves interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been under intense study. Here we report single nuclear RNA sequencing profile of the injured zebrafish heart and identified distinct cardiomyocyte populations in the injured heart. These cardiomyocyte populations indicate diverse functions that includes stress-response, myofibril assembly, proliferation and contraction. The contracting cardiomyocyte population also involves activation of maturation pathways as an early response to injury. This intriguing finding suggests that constant maintenance of distinctive terminally differentiated cardiomyocyte population is important for cardiac function during regeneration. To test this, we determined that cited4a, a p300/CBP transcriptional co-activator, is induced after injury in mature cardiomyocyte population. Moreover, loss-of-cited4a mutants showed increased dedifferentiation, proliferation and accelerated heart regeneration. Thus, suppressing cardiomyocyte maturation pathway activity in injured hearts could be an approach to promote heart regeneration.

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