{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:30:49Z","timestamp":1790814649163,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Heilongjiang Province of China","award":["JQ2021C006"],"award-info":[{"award-number":["JQ2021C006"]}]},{"name":"Natural Science Foundation of Heilongjiang Province of China","award":["2016YFA0100200"],"award-info":[{"award-number":["2016YFA0100200"]}]},{"name":"National Key Research and Development Program of China-Stem cell and Translational Research","award":["JQ2021C006"],"award-info":[{"award-number":["JQ2021C006"]}]},{"name":"National Key Research and Development Program of China-Stem cell and Translational Research","award":["2016YFA0100200"],"award-info":[{"award-number":["2016YFA0100200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although the study on the regulatory mechanism of endothelial differentiation from the perspective of development provides references for endothelial cell (EC) derivation from pluripotent stem cells, incomplete reprogramming and donor-specific epigenetic memory are still thought to be the obstacles of iPSCs for clinical application. Thus, it is necessary to establish a stable iPSC-EC induction system and investigate the regulatory mechanism of endothelial differentiation. Based on a single-layer culture system, we successfully obtained ECs from porcine iPSCs (piPSCs). In vitro, the derived piPSC-ECs formed microvessel-like structures along 3D gelatin scaffolds. Under pathological conditions, the piPSC-ECs functioned on hindlimb ischemia repair by promoting blood vessel formation. To elucidate the molecular events essential for endothelial differentiation in our model, genome-wide transcriptional profile analysis was conducted, and we found that during piPSC-EC derivation, the synthesis and secretion level of TGF-\u03b2 as well as the phosphorylation level of Smad2\/3 changed dynamically. TGF-\u03b2-Smad2\/3 signaling activation promoted mesoderm formation and prevented endothelial differentiation. Understanding the regulatory mechanism of iPSC-EC derivation not only paves the way for further optimization, but also provides reference for establishing a cardiovascular drug screening platform and revealing the molecular mechanism of endothelial dysfunction.<\/jats:p>","DOI":"10.3390\/ijms23137029","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"7029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Derivation and Characterization of Endothelial Cells from Porcine Induced Pluripotent Stem Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Yang","family":"Yu","sequence":"first","affiliation":[{"name":"College of Life Science, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechun","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyue","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-2097","authenticated-orcid":false,"given":"Hai","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9199-6493","authenticated-orcid":false,"given":"Zhonghua","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2291-2022","authenticated-orcid":false,"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Agricultural University, Harbin 150030, China"},{"name":"School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. 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