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- W2917543658 abstract "The mechanistic basis of gliogenesis, which occurs late in human development, is poorly understood. Here we identify nuclear factor IA (NFIA) as a molecular switch inducing human glial competency. Transient expression of NFIA is sufficient to trigger glial competency of human pluripotent stem cell-derived neural stem cells within 5 days and to convert these cells into astrocytes in the presence of glial-promoting factors, as compared to 3–6 months using current protocols. NFIA-induced astrocytes promote synaptogenesis, exhibit neuroprotective properties, display calcium transients in response to appropriate stimuli and engraft in the adult mouse brain. Differentiation involves rapid but reversible chromatin remodeling, glial fibrillary acidic protein (GFAP) promoter demethylation and a striking lengthening of the G1 cell cycle phase. Genetic or pharmacological manipulation of G1 length partially mimics NFIA function. We used the approach to generate astrocytes with region-specific or reactive features. Our study defines key mechanisms of the gliogenic switch and enables the rapid production of human astrocytes for disease modeling and regenerative medicine. A new method generates astrocytes from human pluripotent stem cells in 5 days." @default.
- W2917543658 created "2019-03-02" @default.
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- W2917543658 date "2019-02-25" @default.
- W2917543658 modified "2023-10-06" @default.
- W2917543658 title "NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells" @default.
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- W2917543658 doi "https://doi.org/10.1038/s41587-019-0035-0" @default.
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