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We integrated public single\u2010nucleus RNA\u2010seq, spatial transcriptomics, bulk RNA\u2010seq and ATAC\u2010seq datasets from human fetal hearts and adult infarcted hearts to investigate why cell\u2010cycle\u2010active cardiomyocytes fail to complete division. These cells were enriched in the infarct zone (IZ) and activated early cell\u2010cycle programs, but showed insufficient reactivation of late mitotic and cytokinesis execution machinery, particularly\n                    <jats:italic>ANLN<\/jats:italic>\n                    and\n                    <jats:italic>KIF18A<\/jats:italic>\n                    , and instead engaged stress\u2010adaptive programs. Multi\u2010omics filtering across expression, chromatin accessibility, and co\u2010expression\/regulatory networks highlighted five developmental cell\u2010cycle\u2010associated genes with insufficient adult reactivation:\n                    <jats:italic>ANLN<\/jats:italic>\n                    ,\n                    <jats:italic>KIF18A<\/jats:italic>\n                    ,\n                    <jats:italic>MDK<\/jats:italic>\n                    ,\n                    <jats:italic>RTKN2<\/jats:italic>\n                    , and\n                    <jats:italic>SOX11<\/jats:italic>\n                    . In human induced pluripotent stem cell\u2010derived cardiomyocytes, hypoxia suppressed most candidates, whereas\n                    <jats:italic>MDK<\/jats:italic>\n                    retained responsiveness to pro\u2010proliferative Wnt stimulation. These findings suggest that incomplete cytokinesis reactivation represents a key bottleneck for adult human cardiac regeneration, and nominate\n                    <jats:italic>MDK<\/jats:italic>\n                    as a tractable candidate for chemical biology and drug\u2010discovery efforts aimed at promoting cardiomyocyte cell\u2010cycle completion.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70337","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:49:10Z","timestamp":1780984150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics Integration Reveals Incomplete Reactivation of Developmental Cell\u2010Cycle Programs in Adult Human Infarcted Hearts"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2965-8208","authenticated-orcid":false,"given":"Jieran","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine The University of Osaka  Osaka Japan"},{"name":"Department of Cardiovascular Regenerative Medicine and Drug Discovery, Graduate School of Medicine The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kuramoto","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine The University of Osaka  Osaka Japan"},{"name":"Department of Pathophysiology of Heart Failure and Therapeutics National Cerebral and Cardiovascular Center  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Regenerative Medicine and Drug Discovery, Graduate School of Medicine The University of Osaka  Osaka Japan"},{"name":"Open Innovation Center, Biobank National Cerebral and Cardiovascular Center  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9053-7781","authenticated-orcid":false,"given":"Jong\u2010Kook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Regenerative Medicine and Drug Discovery, Graduate School of Medicine The University of Osaka  Osaka Japan"},{"name":"Faculty of Human Health, Sonoda University  Amagasaki Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Center for Fundamental Education University of Kitakyushu  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine The University of Osaka  Osaka 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