1. Mouse HSA+ immature cardiomyocytes persist in the adult heart and expand after ischemic injury
- Author
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Diana S. Nascimento, Benoit Dupont, Odile Burlen-Defranoux, Francisca Soares-da-Silva, Tatiana P. Resende, Mariana Valente, Ana Cumano, Perpétua Pinto-do-Ó, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Instituto de Investigação e Inovação em Saúde (I3S), Instituto de Engenharia Biomédica (INEB), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Beckman Coulter Genom SA, This work was financed by European Structural and Investment Funds (ESIF), under Lisbon Portugal Regional Operational Program and National Funds through FCT-Foundation for Science and Technology under project POCI-01-0145-FEDER-016385 to PPO, by Pasteur Institute, INSERM, ANR (grant Twothyme), REVIVE Future Investment Program and Pasteur-Weizmann Foundation through grants to AC. MV (SFRH/BD/74218/2010) and TPR (SFRH/BPD/80588/2011) were supported by FCT, and PPO was recipient of an invited scientist grant by Institut Pasteur, Paris, France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-14-CE11-0022,Twothyme,Deux progéniteurs hématopoïétiques différents établissent le compartiment de lymphocytes T: tester un nouveau paradigme du développement T.(2014), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Instituto de Investigação e Inovação em Saúde, Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vougny, Marie-Christine, Appel à projets générique - Deux progéniteurs hématopoïétiques différents établissent le compartiment de lymphocytes T: tester un nouveau paradigme du développement T. - - Twothyme2014 - ANR-14-CE11-0022 - Appel à projets générique - VALID, and Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID
- Subjects
Male ,0301 basic medicine ,Physiology ,Cellular differentiation ,Myocardial Ischemia ,Gene Expression ,Cell Lineage / physiology ,Biochemistry ,Myocytes, Cardiac / metabolism ,Mice ,Spectrum Analysis Techniques ,0302 clinical medicine ,Single-cell analysis ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,Myocyte ,Myocytes, Cardiac ,Flow cytometry ,Biology (General) ,health care economics and organizations ,Cardiomyocytes ,education.field_of_study ,Immune System Proteins ,CD24 ,General Neuroscience ,Cell Differentiation ,Heart ,Cell biology ,Heart / growth & development ,Spectrophotometry ,Myocytes, Cardiac / physiology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Cytophotometry ,Anatomy ,Cellular Types ,Single-Cell Analysis ,General Agricultural and Biological Sciences ,Research Article ,CD24 Antigen / physiology ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Myocardium / metabolism ,QH301-705.5 ,Immunology ,Population ,Cardiology ,Muscle Tissue ,Biology ,Research and Analysis Methods ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,CD24 Antigen / metabolism ,health services administration ,Genetics ,Regeneration ,Animals ,Cell Lineage ,Heart / physiology ,Antigens ,Progenitor cell ,education ,Muscle Cells ,General Immunology and Microbiology ,Cluster of differentiation ,Myocardium ,Biology and Life Sciences ,Proteins ,CD24 Antigen ,Cell adhesion ,Cell Biology ,Molecular Development ,Gene regulation ,Mice, Inbred C57BL ,Transplantation ,Myocardial infarction ,Biological Tissue ,030104 developmental biology ,Myocardial Ischemia / physiopathology ,Regeneration / physiology ,Cardiovascular Anatomy ,Myocardial Ischemia / metabolism ,Adhesion molecules ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The assessment of the regenerative capacity of the heart has been compromised by the lack of surface signatures to characterize cardiomyocytes (CMs). Here, combined multiparametric surface marker analysis with single-cell transcriptional profiling and in vivo transplantation identify the main mouse fetal cardiac populations and their progenitors (PRGs). We found that CMs at different stages of differentiation coexist during development. We identified a population of immature heat stable antigen (HSA)/ cluster of differentiation 24 (CD24)+ CMs that persists throughout life and that, unlike other CM subsets, actively proliferates up to 1 week of age and engrafts cardiac tissue upon transplantation. In the adult heart, a discrete population of HSA/CD24+ CMs appears as mononucleated cells that increase in frequency after infarction. Our work identified cell surface signatures that allow the prospective isolation of CMs at all developmental stages and the detection of a subset of immature CMs throughout life that, although at reduced frequencies, are poised for activation in response to ischemic stimuli. This work opens new perspectives in the understanding and treatment of heart pathologies., This study identifies HSA/CD24 as a unique marker for immature cardiomyocytes, showing that HSA-positive cardiomyocytes persist throughout life, proliferating within the first week after birth and responding to myocardial infarction in the adult by expanding through cell division.
- Published
- 2019