The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“hiPSC-derived astrocytes, which can be generated with a fast protocol in 2D layers104 or integrated in 3D systems such as spheroids and organoids105–108”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [104]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
deepTools2: a next generation web server for deep-sequencing data analysis
Ramírez, F., Ryan, D. P., Grüning, B., Bhardwaj, V., Kilpert, F., Richter, A. S., Heyne, S., Dündar, F., & Manke, T. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw257 · Cited by 8,096
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129
Cited by
Sorted by citations
Reactive astrocyte nomenclature, definitions, and future directions
Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00783-4 · Cited by 2,513
Clark, B. S., Stein-O’Brien, G., Shiau, F., Cannon, G. H., Davis-Marcisak, E. F., Sherman, T. D., Santiago, C. P., Hoang, T. V., Rajaii, F., James-Esposito, R. E., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.010 · Cited by 527
Guttikonda, S. R., Sikkema, L., Tchieu, J. H., Saurat, N. G., Walsh, R. M., Harschnitz, O., Ciceri, G., Sneeboer, M. A. M., Mažutis, L., Setty, M. N., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00796-z · Cited by 249
Self-citationAstrocytes: a double-edged sword in neurodegenerative diseases
Ding, Z.-B., Song, L., Wang, Q., Kumar, G., Yan, Y.-Q., & Kumar, G. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.306064 · Cited by 259
An epigenetic barrier sets the timing of human neuronal maturation
Ciceri, G., Baggiolini, A., Cho, H. S., Kshirsagar, M., Benito-Kwiecinski, S., Walsh, R. M., Aromolaran, K. A., Gonzalez-Hernandez, A. J., Munguba, H., Koo, S. Y., et al. (2024) · Nature · doi:10.1038/s41586-023-06984-8 · Cited by 240
Self-citation
Metadata
- 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
- Venue
- Nature Biotechnology
- Published
- 2019-02-25
- Volume
- 37
- Issue
- 3
- Pages
- 267-275
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
