Year: 2021
Type: article
Abstract: Cardiomyocytes undergo significant structural and functional changes after birth, and these fundamental processes are essential for the heart to pump blood to the growing body. However, due to the challenges of isolating single postnatal/adult myocytes, how individual newborn cardiomyocytes acquire multiple aspects of the mature phenotype remains poorly understood. Here we implement large-particle sorting and analyze single myocytes from neonatal to adult hearts. Early myocytes exhibit wide-ranging transcriptomic and size heterogeneity that is maintained until adulthood with a continuous transcriptomic shift. Gene regulatory network analysis followed by mosaic gene deletion reveals that peroxisome proliferator-activated receptor coactivator-1 signaling, which is active in vivo but inactive in pluripotent stem cell-derived cardiomyocytes, mediates the shift. This signaling simultaneously regulates key aspects of cardiomyocyte maturation through previously unrecognized proteins, including YAP1 and SF3B2. Our study provides a single-cell roadmap of heterogeneous transitions coupled to cellular features and identifies a multifaceted regulator controlling cardiomyocyte maturation.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: U.S. Department of Health and Human Services, American Heart Association, Maryland Stem Cell Research Fund, National Institutes of Health, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Regulation of Cardiac Progenitor Maintenance, Biomedical Engineering Training Program, Leveraging Protein Kinase G-1 Nanodomain Control and Molecular Targeting to Enhance its Therapeutic Use Against Myocardial Disease, Engineering a power switch to study the contribution of stem cell-derived cardiomyocytes on heart regeneration, Discovery of small molecule regulators of atrial cardiomyocyte action potential duration to restore normal cardiac rhythm in atrial fibrillation, Discovery of small molecule promoters of cardiomyocyte proliferation to restore cardiac performance in disease, Comprehensive Platform for Studying Molecular Mechanisms Regulating Cardiomyocyte Maturation, Transcriptomic Entropy to Quantify Maturation of PSC-Derived Cardiomyocytes, Pathophysiology of Myocardial Disease
OpenAlex ID: W3133589067