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In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line using CreER\n                    <jats:sup>T2<\/jats:sup>\n                    technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of the\n                    <jats:italic>Aldh1a1\/a2\/a3<\/jats:italic>\n                    genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals\n                    <jats:italic>Tgm2<\/jats:italic>\n                    and\n                    <jats:italic>Ace1,<\/jats:italic>\n                    two genes with well-established links to cardiac repair\n                    <jats:italic>,<\/jats:italic>\n                    as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.\n                  <\/jats:p>","DOI":"10.7554\/elife.68280","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T10:01:13Z","timestamp":1633687273000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68280","source":"Crossref","is-referenced-by-count":39,"title":["Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8983-2238","authenticated-orcid":true,"given":"Fabio","family":"Da Silva","sequence":"first","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariba","family":"Jian Motamedi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-8946","authenticated-orcid":true,"given":"Lahiru Chamara","family":"Weerasinghe Arachchige","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Tison","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-3894","authenticated-orcid":true,"given":"Stephen T","family":"Bradford","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Dolle","sequence":"additional","affiliation":[{"name":"IGBMC, Inserm U1258, UNISTRA CNRS","place":["Illkirch, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert B","family":"Ghyselinck","sequence":"additional","affiliation":[{"name":"IGBMC, Inserm U1258, UNISTRA CNRS","place":["Illkirch, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay D","family":"Wagner","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9380-7396","authenticated-orcid":true,"given":"Andreas","family":"Schedl","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, Inserm, CNRS, iBV","place":["Nice, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"9526","DOI":"10.1074\/jbc.271.16.9526","article-title":"Retinoic acid synthesis in mouse embryos during gastrulation and craniofacial development linked to class IV alcohol dehydrogenase gene expression","volume":"271","author":"Ang","year":"1996","journal-title":"The Journal of Biological 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