{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:14:17Z","timestamp":1790997257036,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL137204"],"award-info":[{"award-number":["R01 HL137204"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016944","name":"Regenerative Medicine Minnesota","doi-asserted-by":"publisher","award":["RMM 091718"],"award-info":[{"award-number":["RMM 091718"]}],"id":[{"id":"10.13039\/100016944","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016944","name":"Regenerative Medicine Minnesota","doi-asserted-by":"publisher","award":["RMM 091620DS008"],"award-info":[{"award-number":["RMM 091620DS008"]}],"id":[{"id":"10.13039\/100016944","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cardiomyocyte (CM) proliferation and maturation are highly linked processes, however, the extent to which these processes are controlled by a single signaling axis is unclear. Here, we show the previously undescribed role of Hedgehog (HH)-GLI2-CKS1B cascade in regulation of the toggle between CM proliferation and maturation. Here we show downregulation of GLI-signaling in adult human CM, adult murine CM, and in late-stage hiPSC-CM leading to their maturation. In early-stage hiPSC-CM, inhibition of HH- or GLI-proteins enhanced CM maturation with increased maturation indices, increased calcium handling, and transcriptome. Mechanistically, we identified CKS1B, as a new effector of GLI2 in CMs. GLI2 binds the CKS1B promoter to regulate its expression. CKS1B overexpression in late-stage hiPSC-CMs led to increased proliferation with loss of maturation in CMs. Next, analysis of datasets of patients with heart disease showed a significant enrichment of GLI2-signaling in patients with ischemic heart failure (HF) or dilated-cardiomyopathy (DCM) disease, indicating operational GLI2-signaling in the stressed heart. Thus, the Hh-GLI2-CKS1B axis regulates the proliferation-maturation transition and provides targets to enhance cardiac tissue engineering and regenerative therapies.<\/jats:p>","DOI":"10.1093\/stcltm\/szae032","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T06:33:47Z","timestamp":1716014027000},"page":"678-692","source":"Crossref","is-referenced-by-count":10,"title":["The\n                    <i>HH-GLI2-CKS1B<\/i>\n                    network regulates the proliferation-to-maturation transition of cardiomyocytes"],"prefix":"10.1093","volume":"13","author":[{"given":"Christina J","family":"Waldron","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Minnesota , MN 55455 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Minnesota , MN 55455 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Stan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Minnesota , MN 55455 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0043-9705","authenticated-orcid":false,"given":"Yasuhiko","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell Biology and Development, University of Minnesota , MN 55455 , United States"},{"name":"Stem Cell Institute, University of Minnesota , MN 55455 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan E","family":"Abrahante","sequence":"additional","affiliation":[{"name":"University of Minnesota Informatics Institute, University of Minnesota , MN 55455 , United 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