Cardiomyocyte heterogeneity during zebrafish development and regeneration

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Zebrafish Models

Background:

• Zebrafish exhibit remarkable heart regeneration after injury, unlike mammals.
• Cardiomyocytes (CMs) dedifferentiate and proliferate to aid cardiac repair.
• Understanding CM heterogeneity and dynamics is crucial for cardiac regeneration research.

Purpose of the Study:

• To identify and characterize distinct cardiomyocyte populations during zebrafish heart development and regeneration.
• To investigate the role of specific gene markers in defining CM states.
• To explore the involvement of Notch signaling in cardiomyocyte heterogeneity and regeneration.

Main Methods:

• Comparative transcriptomic analysis of developing and adult zebrafish hearts.
• Development and utilization of novel reporter lines for tnnc2 and tnni4b.3 genes.
• In vivo imaging and analysis of reporter gene expression dynamics.
• Transcriptomic profiling of specific cardiomyocyte subpopulations.

Main Results:

• tnnc2 and tnni4b.3 identified as markers for early and late-stage CMs, respectively.
• tnnc2 expression is high in embryonic CMs, declining significantly in adults, while tnni4b.3 expression increases in adult CMs.
• Adult CMs expressing the tnnc2 reporter exhibit immature markers and elevated Notch signaling.
• During regeneration, injured CMs activate the tnnc2 reporter and downregulate tnni4b.3, indicating a shift towards an embryonic-like state.

Conclusions:

• Zebrafish hearts harbor heterogeneous cardiomyocyte populations with distinct developmental origins and molecular signatures.
• The tnnc2 and tnni4b.3 markers provide valuable tools to study CM dynamics.
• Notch signaling is implicated in maintaining immature cardiomyocyte characteristics.
• Regenerating cardiomyocytes in adult zebrafish undergo molecular changes reminiscent of developmental stages.