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Here, using single-cell RNA sequencing analysis of adult zebrafish heart, we identified a unique CM subpopulation marked by the expression of\n                    <jats:italic>phlda2<\/jats:italic>\n                    , which is associated with anaerobic metabolism and different from mature CMs, which are enriched for oxidative phosphorylation genes. We demonstrated that\n                    <jats:italic>phlda2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    cells constituted a primordial CM compartment localized between compact and trabecular muscles. Genetic ablation of\n                    <jats:italic>phlda2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    CMs during development severely disrupted heart morphogenesis, leading to defective myocardial trabeculation and compaction, and impaired coronary vascularization. Surprisingly, despite their essential roles in development, the depletion of\n                    <jats:italic>phlda2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    CMs didn\u2019t impair myocardial restoration and revascularization following ventricular resection. We found that this was probably due to the limited regenerative capacity of the primordial CMs themselves, as they failed to regenerate after either surgical amputation or genetic ablation. Our findings identify primordial CMs as an organizer for heart morphogenesis but not essential for regeneration, revealing a fundamental difference between developmental and regenerative programs in the vertebrate heart.\n                  <\/jats:p>","DOI":"10.7554\/elife.110256","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T14:33:58Z","timestamp":1772634838000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.110256","source":"Crossref","is-referenced-by-count":0,"title":["Primordial cardiomyocytes orchestrate myocardial morphogenesis and vascularization but are dispensable for regeneration"],"prefix":"10.7554","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0814-1118","authenticated-orcid":true,"given":"Jisheng","family":"Sun","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiology Division, Department of Medicine, Emory 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