{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:54:42Z","timestamp":1772985282655,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":352,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070487"],"award-info":[{"award-number":["82070487"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370787"],"award-info":[{"award-number":["32370787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670454"],"award-info":[{"award-number":["81670454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Thoracic aortic dissection (TAD) is a life\u2010threatening condition characterized by medial degeneration and vascular smooth muscle cell (VSMC) dysfunction, with no effective medical therapy currently available. The underlying pathological mechanisms of TAD remain incompletely understood. In this study, we used a nonintegrated episomal vector\u2010based reprograming system to generate induced pluripotent stem cells (iPSCs) from TAD patients and healthy controls. Both TAD and normal iPSCs expressed key pluripotency markers and were capable of differentiating into the three germ layers in vitro. These iPSCs were differentiated into vascular smooth muscle cells (VSMCs) through a mesodermal intermediate for disease modeling. VSMCs derived from both TAD and normal iPSCs expressed smooth muscle\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010actin (\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010SMA), calponin (CNN), and SM22\n                    <jats:italic>\u03b1<\/jats:italic>\n                    . However, TAD\u2013iPSC\u2010derived VSMCs exhibited significantly reduced contraction in response to carbachol stimulation compared to their normal counterparts. Whole\u2010exome sequencing identified a mutation in the COL4A2 gene (c.392G\u2009&gt;\u2009T, p. R131M) in TAD\u2013iPSCs. This mutation was associated with reduced collagen IV expression and increased expression of collagen I and III in TAD\u2010VSMCs, both with and without TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    stimulation. Furthermore, noncanonical TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    signaling was hyperactivated in TAD\u2010VSMCs, accompanied by elevated MMP9 expression. This patient\u2010specific iPSC model reveals key dysfunctions in VSMC contractility, extracellular matrix (ECM) protein expression, and dysregulated TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    signaling, which may contribute to TAD pathogenesis. Our findings provide new insights into the molecular mechanisms driving TAD and offer a platform for future therapeutic development.\n                  <\/jats:p>","DOI":"10.1155\/sci\/4700736","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T05:56:54Z","timestamp":1766210214000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling Thoracic Aortic Dissection Using Patient\u2010Specific iPSCs Reveals VSMC Dysfunction and Extracellular Matrix Dysregulation"],"prefix":"10.1155","volume":"2025","author":[{"given":"Peifeng","family":"Jin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sixian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miqi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiufang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongsheng","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6088-8887","authenticated-orcid":false,"given":"Yongyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.031264"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.53"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac757"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.187"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312436"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-3400233"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01970-5"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.06.007"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq356"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000108263.74520.15"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-4-29"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy006"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16312"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2009.07.075"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1349548"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/HCG.0000000000000043"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.116.013003"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3723"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2020.101730"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604850103"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg2102s87"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.1.66.bloodjournal82166"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2023.01.005"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.303229"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.063332"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds346"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.210"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.156166"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09747"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11799"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.08.003"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-016-0333-3"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071906"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601442113"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq230"},{"key":"e_1_2_14_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311450"},{"key":"e_1_2_14_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4534"},{"key":"e_1_2_14_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.310956"},{"key":"e_1_2_14_39_2","doi-asserted-by":"publisher","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