{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:12:10Z","timestamp":1792419130499,"version":"4.5.0"},"reference-count":176,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["HL135117"],"award-info":[{"award-number":["HL135117"]}]},{"name":"National Institute of Health","award":["20TPA35490355"],"award-info":[{"award-number":["20TPA35490355"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Transformational Project Award","doi-asserted-by":"publisher","award":["HL135117"],"award-info":[{"award-number":["HL135117"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Transformational Project Award","doi-asserted-by":"publisher","award":["20TPA35490355"],"award-info":[{"award-number":["20TPA35490355"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The adult heart is made up of cardiomyocytes (CMs) that maintain pump function but are unable to divide and form new myocytes in response to myocardial injury. In contrast, the developmental cardiac tissue is made up of proliferative CMs that regenerate injured myocardium. In mammals, CMs during development are diploid and mononucleated. In response to cardiac maturation, CMs undergo polyploidization and binucleation associated with CM functional changes. The transition from mononucleation to binucleation coincides with unique metabolic changes and shift in energy generation. Recent studies provide evidence that metabolic reprogramming promotes CM cell cycle reentry and changes in ploidy and nucleation state in the heart that together enhances cardiac structure and function after injury. This review summarizes current literature regarding changes in CM ploidy and nucleation during development, maturation and in response to cardiac injury. Importantly, how metabolism affects CM fate transition between mononucleation and binucleation and its impact on cell cycle progression, proliferation and ability to regenerate the heart will be discussed.<\/jats:p>","DOI":"10.3390\/cells12121571","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T01:38:41Z","timestamp":1686101921000},"page":"1571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cardiomyocyte Ploidy, Metabolic Reprogramming and Heart Repair"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-7893","authenticated-orcid":false,"given":"Andrea","family":"Elia","sequence":"first","affiliation":[{"name":"Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2106-1094","authenticated-orcid":false,"given":"Sadia","family":"Mohsin","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7007-1048","authenticated-orcid":false,"given":"Mohsin","family":"Khan","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"},{"name":"Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1152\/physrev.00032.2006","article-title":"Cardiac Myocyte Cell Cycle Control in Development, Disease, and Regeneration","volume":"87","author":"Ahuja","year":"2007","journal-title":"Physiol. 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