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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,4,17]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>After myocardial infarction in the mammalian heart, millions of cardiomyocytes are lost and replaced by fibrotic scar tissue. While fibrosis is persistent in adult mammals, there are some vertebrates, including zebrafish, with the capacity for regeneration. This process does not occur in the absence of fibrosis. Here we studied subpopulations of collagen-producing cells and analyzed their fate after complete regeneration of the zebrafish myocardium. Our data show that fibroblasts persisted in the regenerated heart but shut down the profibrotic program. While fibrosis could be considered as detrimental to the regeneration process, our study reveals a positive effect on cardiomyocyte proliferation. Accordingly, a fibrotic response can be beneficial for heart regeneration.<\/jats:p>","DOI":"10.1073\/pnas.1716713115","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T16:42:21Z","timestamp":1522687341000},"page":"4188-4193","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":192,"title":["Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart"],"prefix":"10.1073","volume":"115","author":[{"given":"H\u00e9ctor","family":"S\u00e1nchez-Iranzo","sequence":"first","affiliation":[{"name":"Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Galardi-Castilla","sequence":"additional","affiliation":[{"name":"Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Sanz-Morej\u00f3n","sequence":"additional","affiliation":[{"name":"Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain;"},{"name":"Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Gonz\u00e1lez-Rosa","sequence":"additional","affiliation":[{"name":"Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Costa","sequence":"additional","affiliation":[{"name":"Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain;"},{"name":"Centre for Research in Agricultural Genomics (CRAG) Consejo Superior de Investigaciones Cient\u00edfica (CSIC)-Institut de Recerca i Tecnologia Agroalimentaries (IRTA)-Universitat Autonoma de Barcelona (UAB)-Universitat de Barcelona (UB), Campus UAB, 08193 Bellaterra, Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ernst","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Sainz de Aja","sequence":"additional","affiliation":[{"name":"Functional Genomics Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Langa","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-6399","authenticated-orcid":false,"given":"Nadia","family":"Mercader","sequence":"additional","affiliation":[{"name":"Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain;"},{"name":"Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,4,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.115.306565","article-title":"Cardiac fibrosis: The fibroblast awakens","volume":"118","author":"Travers JG","year":"2016","unstructured":"JG Travers, FA Kamal, J Robbins, KE Yutzey, BC Blaxall, Cardiac fibrosis: The fibroblast awakens. Circ Res 118, 1021\u20131040 (2016).","journal-title":"Circ Res"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrcardio.2017.57","article-title":"Redefining the identity of cardiac fibroblasts","volume":"14","author":"Tallquist MD","year":"2017","unstructured":"MD Tallquist, JD Molkentin, Redefining the identity of cardiac fibroblasts. Nat Rev Cardiol 14, 484\u2013491 (2017).","journal-title":"Nat Rev Cardiol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1172\/JCI74783","article-title":"Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis","volume":"124","author":"Moore-Morris T","year":"2014","unstructured":"T Moore-Morris, , Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis. J Clin Invest 124, 2921\u20132934 (2014).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1196\/annals.1420.005","article-title":"Neonatal and adult cardiovascular pathophysiological remodeling and repair: Developmental role of periostin","volume":"1123","author":"Norris RA","year":"2008","unstructured":"RA Norris, , Neonatal and adult cardiovascular pathophysiological remodeling and repair: Developmental role of periostin. Ann N Y Acad Sci 1123, 30\u201340 (2008).","journal-title":"Ann N Y Acad Sci"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1161\/CIRCRESAHA.109.201400","article-title":"Origin of cardiac fibroblasts and the role of periostin","volume":"105","author":"Snider P","year":"2009","unstructured":"P Snider, , Origin of cardiac fibroblasts and the role of periostin. Circ Res 105, 934\u2013947 (2009).","journal-title":"Circ Res"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"12260","DOI":"10.1038\/ncomms12260","article-title":"Genetic lineage tracing defines myofibroblast origin and function in the injured heart","volume":"7","author":"Kanisicak O","year":"2016","unstructured":"O Kanisicak, , Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun 7, 12260 (2016).","journal-title":"Nat Commun"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.scr.2014.07.003","article-title":"Advances in understanding the mechanism of zebrafish heart regeneration","volume":"13","author":"Kikuchi K","year":"2014","unstructured":"K Kikuchi, Advances in understanding the mechanism of zebrafish heart regeneration. Stem Cell Res (Amst) 13, 542\u2013555 (2014).","journal-title":"Stem Cell Res (Amst)"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/reg2.83","article-title":"Zebrafish heart regeneration: 15 years of discoveries","volume":"4","author":"Gonz\u00e1lez-Rosa JM","year":"2017","unstructured":"JM Gonz\u00e1lez-Rosa, CE Burns, CG Burns, Zebrafish heart regeneration: 15 years of discoveries. Regeneration (Oxf) 4, 105\u2013123 (2017).","journal-title":"Regeneration (Oxf)"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1242\/dev.060897","article-title":"Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish","volume":"138","author":"Gonz\u00e1lez-Rosa JM","year":"2011","unstructured":"JM Gonz\u00e1lez-Rosa, V Mart\u00edn, M Peralta, M Torres, N Mercader, Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish. 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