PGC1/PPAR drive cardiomyocyte maturation at single cell level via YAP1 and SF3B2

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Developmental Biology

Background:

• Postnatal cardiomyocyte development is crucial for heart function but poorly understood at the single-cell level.
• Challenges in isolating neonatal and adult cardiomyocytes hinder research into cellular maturation processes.

Purpose of the Study:

• To elucidate the single-cell dynamics of cardiomyocyte maturation from neonatal to adult stages.
• To identify the molecular mechanisms and signaling pathways governing cardiomyocyte phenotype acquisition.

Main Methods:

• Large-particle sorting was used to isolate single cardiomyocytes from neonatal to adult hearts.
• Single-cell transcriptomic analysis revealed heterogeneity and continuous shifts in gene expression.
• Gene regulatory network analysis and mosaic gene deletion identified key signaling pathways and proteins.

Main Results:

• Neonatal cardiomyocytes exhibit significant transcriptomic and size heterogeneity, which persists into adulthood.
• A continuous transcriptomic shift occurs during cardiomyocyte maturation.
• Peroxisome proliferator-activated receptor coactivator-1 (PGC-1) signaling mediates this shift, regulating proteins such as YAP1 and SF3B2.

Conclusions:

• A single-cell roadmap of cardiomyocyte maturation reveals heterogeneous cellular transitions.
• PGC-1 signaling is a critical regulator of cardiomyocyte maturation, acting through novel protein interactions.
• Understanding these mechanisms provides insights into heart development and potential therapeutic targets.