Sánchez-Iranzo, HéctorHéctorSánchez-IranzoGalardi-Castilla, MaríaMaríaGalardi-CastillaSanz Morejon, AndrésAndrésSanz MorejonGonzález-Rosa, Juan ManuelJuan ManuelGonzález-RosaCosta, RicardoRicardoCostaErnst, Alexander Uwe JohannAlexander Uwe JohannErnst0000-0002-4956-315XSainz de Aja, JulioJulioSainz de AjaLanga, XavierXavierLangaMercader Huber, Nadia IsabelNadia IsabelMercader Huber0000-0002-0905-63992024-10-252024-10-252018-04-17https://boris-portal.unibe.ch/handle/20.500.12422/163139In the zebrafish (), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with regrowth of the myocardial wall. Little is known about the cells producing this fibrotic tissue or how it resolves. Using novel genetic tools to mark - and ()-expressing cells in combination with transcriptome analysis, we explored the sources of activated fibroblasts and traced their fate. We describe that during fibrosis regression, fibroblasts are not fully eliminated but become inactivated. Unexpectedly, limiting the fibrotic response by genetic ablation of -expressing cells impaired cardiomyocyte proliferation. We conclude that ECM-producing cells are key players in the regenerative process and suggest that antifibrotic therapies might be less efficient than strategies targeting fibroblast inactivation.encardiomyocyte proliferation fibroblast inactivation fibrosis heart regeneration zebrafish600 - Technology::610 - Medicine & healtharticle10.7892/boris.1182142961034310.1073/pnas.1716713115