PGC1/PPAR drive cardiomyocyte maturation at single cell level via YAP1 and SF3B2. Nat Commun 2021 Mar 12;12(1):1648
Date
03/14/2021Pubmed ID
33712605Pubmed Central ID
PMC7955035DOI
10.1038/s41467-021-21957-zScopus ID
2-s2.0-85102485873 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
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.
Author List
Murphy SA, Miyamoto M, Kervadec A, Kannan S, Tampakakis E, Kambhampati S, Lin BL, Paek S, Andersen P, Lee DI, Zhu R, An SS, Kass DA, Uosaki H, Colas AR, Kwon CAuthor
Brian L. Lin PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Calcium
Cell Cycle Proteins
Cell Differentiation
Gene Regulatory Networks
Humans
Induced Pluripotent Stem Cells
Mice
Myocytes, Cardiac
Peroxisome Proliferator-Activated Receptors
Pluripotent Stem Cells
RNA Splicing Factors
Signal Transduction
Transcription Factors
Transcriptome
