{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:22Z","timestamp":1787028502561,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["383067719"],"award-info":[{"award-number":["383067719"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["RA 2876\/2-2"],"award-info":[{"award-number":["RA 2876\/2-2"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["161L0276"],"award-info":[{"award-number":["161L0276"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["FOVB-2020-01"],"award-info":[{"award-number":["FOVB-2020-01"]}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research (BMBF)","doi-asserted-by":"publisher","award":["383067719"],"award-info":[{"award-number":["383067719"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research (BMBF)","doi-asserted-by":"publisher","award":["RA 2876\/2-2"],"award-info":[{"award-number":["RA 2876\/2-2"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research (BMBF)","doi-asserted-by":"publisher","award":["161L0276"],"award-info":[{"award-number":["161L0276"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research (BMBF)","doi-asserted-by":"publisher","award":["FOVB-2020-01"],"award-info":[{"award-number":["FOVB-2020-01"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Network Molecular Medicine of the University Medicine Greifswald","award":["383067719"],"award-info":[{"award-number":["383067719"]}]},{"name":"Research Network Molecular Medicine of the University Medicine Greifswald","award":["RA 2876\/2-2"],"award-info":[{"award-number":["RA 2876\/2-2"]}]},{"name":"Research Network Molecular Medicine of the University Medicine Greifswald","award":["161L0276"],"award-info":[{"award-number":["161L0276"]}]},{"name":"Research Network Molecular Medicine of the University Medicine Greifswald","award":["FOVB-2020-01"],"award-info":[{"award-number":["FOVB-2020-01"]}]},{"name":"the Gerhard Domagk program of the University Medicine Greifswald","award":["383067719"],"award-info":[{"award-number":["383067719"]}]},{"name":"the Gerhard Domagk program of the University Medicine Greifswald","award":["RA 2876\/2-2"],"award-info":[{"award-number":["RA 2876\/2-2"]}]},{"name":"the Gerhard Domagk program of the University Medicine Greifswald","award":["161L0276"],"award-info":[{"award-number":["161L0276"]}]},{"name":"the Gerhard Domagk program of the University Medicine Greifswald","award":["FOVB-2020-01"],"award-info":[{"award-number":["FOVB-2020-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cerebral cavernous malformation (CCM) is a neurovascular disease that can lead to seizures and stroke-like symptoms. The familial form is caused by a heterozygous germline mutation in either the CCM1, CCM2, or CCM3 gene. While the importance of a second-hit mechanism in CCM development is well established, it is still unclear whether it immediately triggers CCM development or whether additional external factors are required. We here used RNA sequencing to study differential gene expression in CCM1 knockout induced pluripotent stem cells (CCM1\u2212\/\u2212 iPSCs), early mesoderm progenitor cells (eMPCs), and endothelial-like cells (ECs). Notably, CRISPR\/Cas9-mediated inactivation of CCM1 led to hardly any gene expression differences in iPSCs and eMPCs. However, after differentiation into ECs, we found the significant deregulation of signaling pathways well known to be involved in CCM pathogenesis. These data suggest that a microenvironment of proangiogenic cytokines and growth factors can trigger the establishment of a characteristic gene expression signature upon CCM1 inactivation. Consequently, CCM1\u2212\/\u2212 precursor cells may exist that remain silent until entering the endothelial lineage. Collectively, not only downstream consequences of CCM1 ablation but also supporting factors must be addressed in CCM therapy development.<\/jats:p>","DOI":"10.3390\/ijms24043993","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T04:01:52Z","timestamp":1676520112000},"page":"3993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endothelial Differentiation of CCM1 Knockout iPSCs Triggers the Establishment of a Specific Gene Expression Signature"],"prefix":"10.3390","volume":"24","author":[{"given":"Robin A.","family":"Pilz","sequence":"first","affiliation":[{"name":"Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariush","family":"Skowronek","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Mellinger","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-8862","authenticated-orcid":false,"given":"Sander","family":"Bekeschus","sequence":"additional","affiliation":[{"name":"ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Felbor","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, 17475 Greifswald, Germany"},{"name":"Department of Human Medicine and Institute for Molecular Medicine, MSH Medical School Hamburg, 20457 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ejhg.2011.155","article-title":"Cerebral cavernous malformations: From molecular pathogenesis to genetic counselling and clinical management","volume":"20","author":"Haasdijk","year":"2012","journal-title":"Eur. 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