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To address this question in a model of DS neurogenesis, we derived trisomy 21 (T21) human induced pluripotent stem cells (iPSCs) alongside, otherwise, isogenic euploid controls from mosaic DS fibroblasts and equipped one chr21 copy with an inducible\n                    <jats:italic>XIST<\/jats:italic>\n                    transgene. Monoallelic chr21 silencing by\n                    <jats:italic>XIST<\/jats:italic>\n                    is near-complete and irreversible in iPSCs. Differential expression reveals that T21 neural lineages and iPSCs share suppressed translation and mitochondrial pathways and activate cellular stress responses. When\n                    <jats:italic>XIST<\/jats:italic>\n                    is induced before the neural progenitor stage, T21 dosage correction suppresses a pronounced skew toward astrogenesis in neural differentiation. Because our transgene remains inducible in postmitotic T21 neurons and astrocytes, we demonstrate that\n                    <jats:italic>XIST<\/jats:italic>\n                    efficiently represses genes even after terminal differentiation, which will empower exploration of cell type\u2013specific T21 phenotypes that remain responsive to chr21 dosage.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adj0385","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T13:58:50Z","timestamp":1717768730000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["A dynamic in vitro model of Down syndrome neurogenesis with trisomy 21 gene dosage correction"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4557-7423","authenticated-orcid":true,"given":"Prakhar","family":"Bansal","sequence":"first","affiliation":[{"name":"Graduate Program in Genetics and 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