Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation

• DOI: 10.1038/s41467-020-16204-w
• Publication Date: 2020-05-22T10:03:39Z
• Authors: Yin Wang; Fang Yao; Lipeng Wang; Zheng Li; Zongna Ren; Dandan Li; Mingzhi Zhang; Leng Han; Shi-qiang Wang; Bingying Zhou; Li Wang
• Keywords: Heart development; Embryonic heart

Abstract Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about contributions of microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data mouse hearts at multiple stages, we construct cellular interactomes regulatory signaling networks. Here report switching fibroblast subtypes from a neonatal adult state this drives Molecular functional cardiomyocytes human embryonic stem cell-derived are considerably enhanced upon co-culture with corresponding cardiac fibroblasts. Further, analysis in vivo vitro trajectories identify highly conserved pathways, pharmacological targeting which substantially delays hearts, markedly enhances proliferation improves function infarcted hearts. Together, fibroblasts as key constituent promoting maturation, providing insights into how manipulation maturity may impact on disease regeneration.