{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:11:30Z","timestamp":1791443490356,"version":"4.3.3"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Most organs are maintained lifelong by resident stem\/progenitor cells. During development and regeneration, lineage-specific stem\/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem\/progenitor cells with EC-repopulating potential residing in blood vessels. It has been reported recently that some EC populations possess higher clonal proliferative potential and vessel-forming capacity compared with mature ECs. Nevertheless, a marker to identify vascular clonal repopulating ECs (CRECs) in murine and human individuals is lacking, and, hence, the mechanism for the proliferative, self-renewal, and vessel-forming potential of CRECs is elusive.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We analyzed colony-forming, self-renewal, and vessel-forming potential of ABCG2 (ATP binding cassette subfamily G member 2)\u2013expressing ECs in human umbilical vessels. To study the contribution of\n              <jats:italic toggle=\"yes\">Abcg2<\/jats:italic>\n              -expressing ECs to vessel development and regeneration, we developed Abcg2Cre\n              <jats:sup>Ert2<\/jats:sup>\n              ;ROSA TdTomato mice and performed lineage tracing during mouse development and during tissue regeneration after myocardial infarction injury. RNA sequencing and chromatin methylation chromatin immunoprecipitation followed by sequencing were conducted to study the gene regulation in\n              <jats:italic toggle=\"yes\">Abcg2<\/jats:italic>\n              -expressing ECs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              In human and mouse vessels, ECs with higher\n              <jats:italic toggle=\"yes\">ABCG2<\/jats:italic>\n              expression (ABCECs) possess higher clonal proliferative potential and in vivo vessel-forming potential compared with mature ECs. These cells could clonally contribute to vessel formation in primary and secondary recipients after transplantation. These features of ABCECs meet the criteria of CRECs. Results from lineage tracing experiments confirm that\n              <jats:italic toggle=\"yes\">Abcg2<\/jats:italic>\n              -expressing CRECs (\n              <jats:italic toggle=\"yes\">Abc<\/jats:italic>\n              CRECs) contribute to arteries, veins, and capillaries in cardiac tissue development and vascular tissue regeneration after myocardial infarction. Transcriptome and epigenetic analyses reveal that a gene expression signature involved in angiogenesis and vessel development is enriched in\n              <jats:italic toggle=\"yes\">Abc<\/jats:italic>\n              CRECs. In addition, various angiogenic genes, such as\n              <jats:italic toggle=\"yes\">Notch2<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">Hey2<\/jats:italic>\n              , are bivalently modified by trimethylation at the 4th and 27th lysine residue of histone H3 (H3K4me3 and H3K27me3) in\n              <jats:italic toggle=\"yes\">Abc<\/jats:italic>\n              CRECs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>These results are the first to establish that a single prospective marker identifies CRECs in mice and human individuals, which holds promise to provide new cell therapies for repair of damaged vessels in patients with endothelial dysfunction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.122.061833","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T09:00:33Z","timestamp":1714381233000},"page":"451-465","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels"],"prefix":"10.1161","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-2468","authenticated-orcid":true,"given":"Yang","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine (Y. Lin, M. Yokoyama, Y. Liu, M.S., M.G., K.C., F.G., J.M.G.S., R.S., D.R., S.R.), Weill Cornell Medicine, New York, NY."},{"name":"Department of Pediatrics, Herman B. Wells Center for Pediatric Research (Y. Lin, C.-H.G., K.B., E.G., N.P., S.C., W.C.S., M. Yoshimoto, M.C.Y.), Indiana University School of Medicine, Indianapolis."},{"name":"Departments of Biochemistry and Molecular Biology (Y. Lin, S.C., M.C.Y.), Indiana University School of Medicine, Indianapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8323-5064","authenticated-orcid":true,"given":"Chang-Hyun","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B. Wells Center for Pediatric Research (Y. Lin, C.-H.G., K.B., E.G., N.P., S.C., W.C.S., M. Yoshimoto, M.C.Y.), Indiana University School of Medicine, Indianapolis."},{"name":"Surgery (C.-H.G., M.P.M.), Indiana University School of Medicine, Indianapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1458-0881","authenticated-orcid":true,"given":"Kimihiko","family":"Banno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B. Wells Center for Pediatric Research (Y. Lin, C.-H.G., K.B., E.G., N.P., S.C., W.C.S., M. Yoshimoto, M.C.Y.), Indiana University School of Medicine, Indianapolis."},{"name":"Department of Physiology II, Nara Medical University, Kashihara, Nara, Japan (K.B., K.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine (Y. Lin, M. Yokoyama, Y. Liu, M.S., M.G., K.C., F.G., J.M.G.S., R.S., D.R., S.R.), Weill Cornell Medicine, New York, NY."},{"name":"Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Japan (M. Yokoyama)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-9605","authenticated-orcid":true,"given":"Matthew","family":"Wingo","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery (M.W.), Weill Cornell Medicine, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-3047","authenticated-orcid":true,"given":"Ellen","family":"Go","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B. Wells Center for Pediatric Research (Y. Lin, C.-H.G., K.B., E.G., N.P., S.C., W.C.S., M. Yoshimoto, M.C.Y.), Indiana University School of Medicine, Indianapolis."},{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (E.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nutan","family":"Prasain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B. Wells Center for Pediatric Research (Y. Lin, C.-H.G., K.B., E.G., N.P., S.C., W.C.S., M. Yoshimoto, M.C.Y.), Indiana University School of Medicine, Indianapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3672-9621","authenticated-orcid":true,"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine (Y. Lin, M. Yokoyama, Y. 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