{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:13:30Z","timestamp":1786965210678,"version":"build-2736575974"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01HL148599"],"award-info":[{"award-number":["R01HL148599"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["P01HL160476"],"award-info":[{"award-number":["P01HL160476"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Congenital heart disease (CHD) is the most common genetic birth defect, which has considerable morbidity and mortality. We focused on deciphering key regulators that govern cardiac progenitors and cardiogenesis. FOXK1 is a forkhead\/winged helix transcription factor known to regulate cell cycle kinetics and is restricted to mesodermal progenitors, somites, and heart. In the present study, we define an essential role for FOXK1 during cardiovascular development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We used the mouse embryoid body system to differentiate control and Foxk1 KO embryonic stem cells into mesodermal, cardiac progenitor cells and mature cardiac cells. Using flow cytometry, immunohistochemistry, cardiac beating, transcriptional and chromatin immunoprecipitation quantitative polymerase chain reaction assays, bulk RNA sequencing (RNAseq) and assay for transposase-accessible chromatin using sequencing (ATACseq) analyses, FOXK1 was observed to be an important regulator of cardiogenesis. Flow cytometry analyses revealed perturbed cardiogenesis in Foxk1 KO embryoid bodies (EBs). Bulk RNAseq analysis at two developmental stages showed a significant reduction of the cardiac molecular program in Foxk1 KO EBs compared to the control EBs. ATACseq analysis during EB differentiation demonstrated that the chromatin landscape nearby known important regulators of cardiogenesis was significantly relaxed in control EBs compared to Foxk1 KO EBs. Furthermore, we demonstrated that in the absence of FOXK1, cardiac differentiation was markedly impaired by assaying for cardiac Troponin T expression and cardiac contractility. We demonstrate that FOXK1 is an important regulator of cardiogenesis by repressing the Wnt\/\u03b2-catenin signalling pathway and thereby promoting differentiation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These results identify FOXK1 as an essential transcriptional and epigenetic regulator of cardiovascular development. Mechanistically, FOXK1 represses Wnt signalling to promote the development of cardiac progenitor cells.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad054","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T16:37:56Z","timestamp":1681144676000},"page":"1728-1739","source":"Crossref","is-referenced-by-count":25,"title":["FOXK1 regulates Wnt signalling to promote cardiogenesis"],"prefix":"10.1093","volume":"119","author":[{"given":"Javier E","family":"Sierra-Pagan","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Dsouza","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyabrata","family":"Das","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thijs A","family":"Larson","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob R","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ma","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Stan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik J","family":"Wanberg","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College, Nanchang University , Nanchang, Jiangxi 330006 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary G","family":"Garry","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"},{"name":"Stem Cell Institute, University of Minnesota , 2001 6th Street SE Minneapolis, MN 55455 , USA"},{"name":"Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota , 516 Delaware ST SE Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuming","family":"Gong","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Garry","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota , 401 East River ParkwayVCRC 1st Floor, Suite 131 Minneapolis, MN 55455 , USA"},{"name":"Stem Cell Institute, University of Minnesota , 2001 6th Street SE Minneapolis, MN 55455 , USA"},{"name":"Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota , 516 Delaware ST SE Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"2023070619360142700_cvad054-B1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00801907","article-title":"Incidence of congenital heart disease: I. 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