{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:06:02Z","timestamp":1777367162510,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G &gt; A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR\/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-\u03baB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.<\/jats:p>","DOI":"10.3390\/ijms22052381","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T20:55:44Z","timestamp":1614459344000},"page":"2381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR\/Cas9-Corrected Mutation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-1938","authenticated-orcid":false,"given":"Hui-Yung","family":"Song","sequence":"first","affiliation":[{"name":"Central Region Laboratory, Center for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei 11561, Taiwan"},{"name":"Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Institute of Pharmacology, National Yang-Ming Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Critical Center, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-9252","authenticated-orcid":false,"given":"Yueh","family":"Chien","sequence":"additional","affiliation":[{"name":"Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Institute of Pharmacology, National Yang-Ming Chiao Tung University, Hsinchu 30010, Taiwan"},{"name":"School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"School of Medicine, National Yang-Ming Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Yi","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Pharmacology, 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Center, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Institute of Food Safety and Health Risk Assessment, National Yang-Ming Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"School of Medicine, National Yang-Ming Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Bang","family":"Leu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Institute of Pharmacology, National Yang-Ming Chiao Tung 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