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However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR\/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1\u03b1-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1\u03b1 in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1\u03b1 deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1\u03b1, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1\u03b1 in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.<\/jats:p>","DOI":"10.1093\/procel\/pwad027","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T02:10:06Z","timestamp":1683771006000},"page":"36-51","source":"Crossref","is-referenced-by-count":16,"title":["Human ESC-derived vascular cells promote vascular regeneration in a HIF-1\u03b1 dependent manner"],"prefix":"10.1093","volume":"15","author":[{"given":"Jinghui","family":"Lei","sequence":"first","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jing","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Yang","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Geng","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Institute for Stem Cell and Regeneration, CAS , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangshuo","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Fifth People\u2019s Hospital of Chongqing , Chongqing 400062 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"},{"name":"National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"},{"name":"Institute for Stem Cell and Regeneration, CAS , Beijing 100101 , China"},{"name":"CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"China National Center for Bioinformation , Beijing 100101 , China"},{"name":"Sino-Danish College, University of Chinese Academy of Sciences , Beijing 101408 , China"},{"name":"Sino-Danish Center for Education and Research , Beijing 101408 , China"},{"name":"Aging Biomarker Consortium , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos Izpisua","family":"Belmonte","sequence":"additional","affiliation":[{"name":"Altos Labs , San Diego, CA 92121 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9289-8177","authenticated-orcid":false,"given":"Guang-Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China"},{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"},{"name":"Institute for Stem Cell and Regeneration, CAS , Beijing 100101 , China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101 , China"},{"name":"Aging Biomarker Consortium , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"2024010310461569400_CIT0001","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/icb.1997.68","article-title":"The role of CD45 and CD45-associated molecules in T cell activation","volume":"75","author":"Altin","year":"1997","journal-title":"Immunol Cell 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