{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:37Z","timestamp":1792787617840,"version":"4.5.0"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32270872,92468103"],"award-info":[{"award-number":["32270872,92468103"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    The endocardium is a major source of coronary angiogenesis and arterialization, through coordinated cell fate transition and migration. However, the transcriptional regulatory network synchronizing cell fate determination and movement remains unclear. Here, we identified transcription factor HAND2 as a key candidate for coronary vascular formation. Endocardial deletion of\n                    <jats:italic>Hand2<\/jats:italic>\n                    in mice disrupted arterial-venous networks and stunted coronary arteries, paralleling a ventricular noncompaction phenotype. Moreover, deletion of\n                    <jats:italic>Hand2<\/jats:italic>\n                    produced excessive tip cells with defective movement. RNA-seq analysis revealed enhanced hypoxic metabolic activation but declined TGF-\u03b2\/p38MAPK\u2013dependent endothelial-mesenchymal transition. In contrast, genetic inhibition of the core hypoxic regulators or pharmaceutical administration of TGF-\u03b22 partially recovered the coronary arterial defects in\n                    <jats:italic>Hand2<\/jats:italic>\n                    mutants. Furthermore, HAND2 was found to directly bind to promoters of the target genes, harmonizing cell migration and cell fate transition. These findings pinpoint HAND2 as an essential regulator of the endocardial transcriptional regulatory network for coronary arterialization and provide potential therapeutic targets for coronary artery diseases.\n                  <\/jats:p>","DOI":"10.1172\/jci203310","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T20:11:41Z","timestamp":1786047101000},"source":"Crossref","is-referenced-by-count":0,"title":["Endocardial transcription factor HAND2 orchestrates hypoxic and TGF-\u03b2 signaling to modulate coronary artery formation"],"prefix":"10.1172","volume":"136","author":[{"given":"Huijuan","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Modern Biology (IMB), Department of Vascular Surgery, Cardiovascular Medical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"IMB, Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiyin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Modern Biology (IMB), Department of Vascular Surgery, Cardiovascular Medical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Modern Biology (IMB), Department of Vascular Surgery, Cardiovascular Medical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Modern Biology (IMB), Department of Vascular Surgery, Cardiovascular Medical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Modern Biology (IMB), Department of Vascular Surgery, Cardiovascular Medical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenping","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Modern Biology (IMB), Department of Vascular Surgery, Cardiovascular Medical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanming","family":"Cheng","sequence":"additional","affiliation":[{"name":"IMB, Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, China."},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhou","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China."},{"name":"Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Modern Biology (IMB), Department of Vascular Surgery, Cardiovascular Medical Center, and"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12422"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.01.021"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000141429.13560.cb"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113736"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307202"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312136"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1242\/dev.131425"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd9050122"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1113\/JP276758"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.857581"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.10.023"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.320335"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2023.03.009"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0400-1"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2022.03.009"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.323474"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49977"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.10.007"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00436-y"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050635"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab298"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58722-5"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/ar.23910"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.11.021"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1242\/dev.201341"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00747-1"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308749"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10239-4"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37409-9"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02796-3"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319955"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-021-10128-3"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.05.096"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.004"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-021-00186-3"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.324868"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/289243"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202490200"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23769"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8856"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.02.122"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.180083"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.02.001"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.233171"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1242\/dev.177477"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-024-00574-1"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2866"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1242\/dev.106336"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2436"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1534\/g3.115.026518"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.09.007"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61537"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.08.008"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-022-00486-z"},{"issue":"15","key":"B56","first-page":"4010","article-title":"Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth","volume":"60","author":"Ryan","year":"2000","journal-title":"Cancer Res"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608382104"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.4.1583"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1242\/dev.093351"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20367"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nature09002"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-3018-x"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/203310\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:01:53Z","timestamp":1790791313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/203310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":62,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1172\/JCI203310"],"URL":"https:\/\/doi.org\/10.1172\/jci203310","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]},"article-number":"e203310"}}