Single-Cell Analysis of Murine Fibroblasts Identifies Neonatal to Adult Switching That Regulates Cardiomyocyte Maturation

This study used single-cell RNA-sequencing to analyze mouse hearts at various postnatal stages, revealing that the transition of fibroblast subtypes from neonatal to adult states played a crucial role in cardiomyocyte maturation. The research demonstrated that co-culturing neonatal mouse cardiomyocytes and human embryonic stem cell-derived cardiomyocytes with adult cardiac fibroblasts significantly enhanced their molecular and functional maturation. Additionally, the study identified conserved signaling pathways that, when pharmacologically targeted, delayed cardiomyocyte maturation, increased proliferation, and improved cardiac function in infarcted hearts. The findings highlighted the importance of cardiac fibroblasts in the microenvironment for promoting cardiomyocyte maturation, offering insights into potential therapeutic strategies for heart disease and regeneration.