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Although a neurogenic-to-gliogenic shift in the fate-specification step has been reported, the mechanisms and key regulators underlying the accelerated proliferation of astrocyte precursor cells (APCs) in DS remain elusive. Here, we established a human isogenic cell line panel based on DS-specific induced pluripotent stem cells, the\n                    <jats:italic>XIST<\/jats:italic>\n                    -mediated transcriptional silencing system in trisomic chromosome 21, and genome\/chromosome-editing technologies to eliminate phenotypic fluctuations caused by genetic variation. The transcriptional responses of genes observed upon\n                    <jats:italic>XIST<\/jats:italic>\n                    induction and\/or downregulation are not uniform, and only a small subset of genes show a characteristic expression pattern, which is consistent with the proliferative phenotypes of DS APCs. Comparative analysis and experimental verification using gene modification reveal dose-dependent proliferation-promoting activity of\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    and\n                    <jats:italic>PIGP<\/jats:italic>\n                    on DS APCs. Our collection of human isogenic cell lines provides a comprehensive set of cellular models for further DS investigations.\n                  <\/jats:p>","DOI":"10.1038\/s42003-021-02242-7","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T06:02:37Z","timestamp":1623650557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome"],"prefix":"10.1038","volume":"4","author":[{"given":"Keiji","family":"Kawatani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Nambara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-7867","authenticated-orcid":false,"given":"Nobutoshi","family":"Nawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Yoshimatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna","family":"Kusakabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-9892","authenticated-orcid":false,"given":"Katsuya","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Tanave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-5439","authenticated-orcid":false,"given":"Kenta","family":"Sumiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiko","family":"Banno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1015-7760","authenticated-orcid":false,"given":"Hidetoshi","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Arahori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Ozono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-9512","authenticated-orcid":false,"given":"Yasuji","family":"Kitabatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"2242_CR1","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrg2538","volume":"10","author":"JM Vaquerizas","year":"2009","unstructured":"Vaquerizas, J. 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