Interplay of cell–cell contacts and RhoA/MRTF‐A signaling regulates cardiomyocyte identity

• Tatjana Dorn ^[1] ; Jessica Kornherr ^[1] ; Elvira I Parrotta ^[1] ; Dorota Zawada ^[1] ; Harold Ayetey ^[5] ; Gianluca Santamaria ^[2] ; Laura Iop ^[1] ; Elisa Mastantuono ^[6] ; Daniel Sinnecker ^[1] ; Alexander Goedel ^[1] ; Ralf J Dirschinger ^[1] ; Ilaria My ^[1] ; Svenja Laue ^[1] ; Tarik Bozoglu ^[1] ; Christian Baarlink ^[3] ; Tilman Ziegler ^[1] ; Elisabeth Graf ^[6] ; Rabea Hinkel ^[1] ; Giovanni Cuda ^[2] ; Stefan Kääb ^[7] ; Andrew A Grace ^[4] ; Robert Grosse ^[3] ; Christian Kupatt ^[1] ; Thomas Meitinger ^[6] ; Austin G Smith ^[8] ; Karl‐Ludwig Laugwitz ^[1] ; Alessandra Moretti ^[1]
  1. [1] Technical University Munich

     Technical University Munich

     Kreisfreie Stadt München, Alemania

     
  2. [2] Magna Graecia University

     Magna Graecia University

     Catanzaro, Italia

     
  3. [3] Philipp University of Marburg

     Philipp University of Marburg

     Landkreis Marburg-Biedenkopf, Alemania

     
  4. [4] Papworth Hospital NHS Foundation Trust

     Papworth Hospital NHS Foundation Trust

     Cambridge District, Reino Unido

     
  5. [5] 3 Wellcome Trust – Medical Research Council Stem Cell Institute University of Cambridge Cambridge UK; 4 Papworth Hospital NHS Foundation Trust Cambridge UK
  6. [6] 5 Institute of Human Genetics Klinikum rechts der Isar – Technical University of Munich Munich Germany
  7. [7] 9 Medizinische Klinik und Poliklinik I Klinikum der Universität München – Ludwig‐Maximillians‐Universität Munich Germany
  8. [8] 3 Wellcome Trust – Medical Research Council Stem Cell Institute University of Cambridge Cambridge UK; 10 Department of Biochemistry University of Cambridge Cambridge UK

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 12, 2018, págs. 1-1
• Idioma: inglés
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  • Cell–cell and cell–matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell–cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA‐ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis‐inducing signals. We also demonstrate by in vivo fate mapping and clonal analysis of cardiac progenitors that cardiac fat and a subset of cardiac muscle arise from a common precursor expressing Isl1 and Wt1 during heart development, suggesting related mechanisms of determination between the two lineages.