Cited by 238Pluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanismsGlioma Diagnosis and Treatment

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NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells

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Tchieu, Jason, Calder, Elizabeth L., Guttikonda, Sudha R., Gutzwiller, Eveline M., Aromolaran, Kelly A., Steinbeck, Julius A., Goldstein, Peter A., Studer, Lorenz·2019·Nature Biotechnology

DOI 10.1038/s41587-019-0035-0PMC PMC6591152

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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.

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Authors: Tchieu, J., Calder, E. L., Guttikonda, S. R., Gutzwiller, E. M., Aromolaran, K. A., Steinbeck, J. A., Goldstein, P. A., & Studer, L.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Weill Cornell Medicine (US)
Corresponding author: Tchieu, Jason
Studer, Lorenz
ORCID: Tchieu, Jason
Gutzwiller, Eveline M.
Goldstein, Peter A.
Studer, Lorenz
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2019-02-25
Volume: 37
Issue: 3
Pages: 267-275
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/s41587-019-0035-0
PMC: PMC6591152
OpenAlex: W2917543658
Cited by: 231
References: 64
Citations by year: 2026: 24 · 2025: 47 · 2024: 40 · 2023: 28 · 2022: 26 · 2021: 33 · 2020: 24 · 2019: 9
FWCI: 7.54
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Biotechnology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Memorial Sloan-Kettering Cancer Center
National Institute on Aging (R01AG056298, R01AG054720)
National Institute of Mental Health (F30MH115616)
National Cancer Institute (P30CA008748)
National Institute of General Medical Sciences (T32GM007739)
National Institute of Neurological Disorders and Stroke (R21NS084334)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
Keywords: NFIA, gliogenesis, astrocyte differentiation, pluripotent stem cells, neural stem cells, chromatin remodeling, synaptogenesis, neuroprotection, reactive astrocytes, disease modeling, regenerative medicine
MeSH terms: Animals, Astrocytes, Cell Differentiation, Humans, Neuroglia, Neurons, Promoter Regions, Genetic, Gene Expression Regulation, Developmental, Pluripotent Stem Cells, Mice, NFI Transcription Factors, Neurogenesis, Neural Stem Cells

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NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells

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