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
Reactive Astrocytes: Production, Function, and Therapeutic Potential
Liddelow, S. A., & Barres, B. A. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.006 · Cited by 2,336
Zhang, Y., Sloan, S. A., Clarke, L. E., Caneda, C., Plaza, C. A., Blumenthal, P. D., Vogel, H., Steinberg, G. K., Edwards, M. S. B., Li, G., et al. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.013 · Cited by 2,295
Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression
Sakaue-Sawano, A., Kurokawa, H., Morimura, T., Hanyu, A., Hama, H., Osawa, H., Kashiwagi, S., Fukami, K., Miyata, T., Miyoshi, H., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.033 · Cited by 2,194
Glutamate Induces Calcium Waves in Cultured Astrocytes: Long-Range Glial Signaling
Cornell-Bell, A. H., Finkbeiner, S. M., Cooper, M. S., & Smith, S. J. (1990) · Science · doi:10.1126/science.1967852 · Cited by 1,846
Uniquely Hominid Features of Adult Human Astrocytes
Oberheim, N. A., Takano, T., Han, X., He, W., Lin, J. H. C., Wang, F., Xu, Q., Wyatt, J. D., Pilcher, W., Ojemann, J. G., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4707-08.2009 · Cited by 1,488
Control of Synapse Number by Glia
Ullian, E. M., Sapperstein, S. K., Christopherson, K. S., & Barres, B. A. (2001) · Science · doi:10.1126/science.291.5504.657 · Cited by 1,380
Astrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202
Cell Biology of Astrocyte-Synapse Interactions
Allen, N. J., & Eroglu, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.056 · Cited by 1,098
Application of a translational profiling approach for the comparative analysis of CNS cell types
Doyle, J. P., Dougherty, J. D., Heiman, M., Schmidt, E. F., Stevens, T. R., Ma, G., Bupp, S., Shrestha, P., Shah, R. D., Doughty, M. L., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.029 · Cited by 912
Astrocytes and disease: a neurodevelopmental perspective
Molofsky, A. V., Krenick, R., Ullian, E., Tsai, H.-H., Deneen, B., Richardson, W. D., Barres, B. A., & Rowitch, D. H. (2012) · Genes & Development · doi:10.1101/gad.188326.112 · Cited by 682
Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage
Elkabetz, Y., Panagiotakos, G., Al Shamy, G., Socci, N. D., Tabar, V., & Studer, L. (2008) · Genes & Development · doi:10.1101/gad.1616208 · Cited by 677
Self-citationThe cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall
Takahashi, T., Nowakowski, R. S., & Caviness, V. S. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-09-06046.1995 · Cited by 673
The Sox9 transcription factor determines glial fate choice in the developing spinal cord
Stolt, C. C., Lommes, P., Sock, E., Chaboissier, M.-C., Schedl, A., & Wegner, M. (2003) · Genes & Development · doi:10.1101/gad.259003 · Cited by 636
TGF-β Family Signaling in the Control of Cell Proliferation and Survival
Zhang, Y., Alexander, P. B., & Wang, X.-F. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022145 · Cited by 626
The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity
Pauklin, S., & Vallier, L. (2013) · Cell · doi:10.1016/j.cell.2013.08.031 · Cited by 611
Maroof, A. M., Keros, S., Tyson, J. A., Ying, S.-W., Ganat, Y. M., Merkle, F. T., Liu, B., Goulburn, A., Stanley, E. G., Elefanty, A. G., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.04.008 · Cited by 596
Self-citationThe transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord
Deneen, B., Ho, R., Lukaszewicz, A., Hochstim, C. J., Gronostajski, R. M., & Anderson, D. J. (2006) · Neuron · doi:10.1016/j.neuron.2006.11.019 · Cited by 514
Koch, P., Opitz, T., Steinbeck, J. A., Ladewig, J., & Brüstle, O. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808387106 · Cited by 508
Self-citationThe Transcriptome and Metabolic Gene Signature of Protoplasmic Astrocytes in the Adult Murine Cortex
Lovatt, D., Sonnewald, U., Waagepetersen, H. S., Schousboe, A., He, W., Lin, J. H.-C., Han, X., Takano, T., Wang, S., Sim, F. J., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3404-07.2007 · Cited by 505
Hirabayashi, Y., Suzki, N., Tsuboi, M., Endo, T. A., Toyoda, T., Shinga, J., Koseki, H., Vidal, M., & Gotoh, Y. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.021 · Cited by 462
An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells
TCW, J., Wang, M., Pimenova, A. A., Bowles, K. R., Hartley, B. J., Lacin, E., Machlovi, S. I., Abdelaal, R., Karch, C. M., Phatnani, H., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.06.018 · Cited by 435
Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release
Betz, A., Ashery, U., Rickmann, M., Augustin, I., Neher, E., Südhof, T. C., Rettig, J., & Brose, N. (1998) · Neuron · doi:10.1016/s0896-6273(00)80520-6 · Cited by 425
Specification of transplantable astroglial subtypes from human pluripotent stem cells
Krencik, R., Weick, J. P., Liu, Y., Zhang, Z., & Zhang, S. (2011) · Nature Biotechnology · doi:10.1038/nbt.1877 · Cited by 410
Multiple Routes to Astrocytic Differentiation in the CNS
Rajan, P., & McKay, R. D. G. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-10-03620.1998 · Cited by 388
Molecular mechanisms controlling cortical gliogenesis.
Sauvageot, C., & Stiles, C. (2002) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(02)00322-7 · Cited by 373
Calegari, F., & Huttner, W. Β. (2003) · Journal of Cell Science · doi:10.1242/jcs.00825 · Cited by 367
APC/C and SCF: Controlling Each Other and the Cell Cycle
Vodermaier, H. C. (2004) · Current Biology · doi:10.1016/j.cub.2004.09.020 · Cited by 323
Modeling ALS with iPSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons
Chen, H., Qian, K., Du, Z., Cao, J., Petersen, A., Liu, H., Blackbourn, L. W., Huang, C.-L., Errigo, A., Yin, Y., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.004 · Cited by 318
The Transcription Factor Gene Nfib Is Essential for both Lung Maturation and Brain Development
Steele-Perkins, G., Plachez, C., Butz, K. G., Yang, G., Bachurski, C. J., Kinsman, S. L., Litwack, E. D., Richards, L. J., & Gronostajski, R. M. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.2.685-698.2005 · Cited by 310
Modeling ALS with motor neurons derived from human induced pluripotent stem cells
Sances, S., Bruijn, L. I., Chandran, S., Eggan, K., Ho, R., Klim, J. R., Livesey, M. R., Lowry, E., Macklis, J. D., Rushton, D., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4273 · Cited by 289
Neural Subtype Specification from Human Pluripotent Stem Cells
Tao, Y., & Zhang, S.-C. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.10.015 · Cited by 287
Naka, H., Nakamura, S., Shimazaki, T., & Okano, H. (2008) · Nature Neuroscience · doi:10.1038/nn.2168 · Cited by 243
das Neves, L., Duchala, C. S., Godinho, F., Haxhiu, M. A., Colmenares, C., Macklin, W. B., Campbell, C. E., Butz, K. G., & Gronostajski, R. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.21.11946 · Cited by 236
A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages
Tchieu, J., Zimmer, B., Fattahi, F., Amin, S., Zeltner, N., Chen, S., & Studer, L. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2017.08.015 · Cited by 235
Self-citationRapid and efficient induction of functional astrocytes from human pluripotent stem cells
Canals, I., Ginisty, A., Quist, E., Timmerman, R., Fritze, J., Miskinyte, G., Monni, E., Hansen, M. G., Hidalgo, I., Bryder, D., et al. (2018) · Nature Methods · doi:10.1038/s41592-018-0103-2 · Cited by 217
CD44 expression identifies astrocyte-restricted precursor cells
Liu, Y., Han, S. S. W., Wu, Y., Tuohy, T. M. F., Xue, H., Cai, J., Back, S. A., Sherman, L. S., Fischer, I., & Rao, M. S. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.08.018 · Cited by 215
Williams, E. C., Zhong, X., Mohamed, A., Li, R., Liu, Y., Dong, Q., Ananiev, G. E., Mok, J. C. C., Lin, B. R., Lü, J., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu008 · Cited by 208
Programming and Reprogramming Cellular Age in the Era of Induced Pluripotency
Studer, L., Vera, E., & Cornacchia, D. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.05.004 · Cited by 192
Self-citationChandrasekaran, A., Avci, H. X., Leist, M., Kobolák, J., & Dinnyés, A. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00215 · Cited by 159
Santos, R., Vadodaria, K. C., Jaeger, B. N., Mei, A., Lefcochilos-Fogelquist, S., Mendes, A. P. D., Erikson, G. A., Shokhirev, M. N., Randolph‐Moore, L., Fredlender, C., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.05.011 · Cited by 142
Functional Connectivity under Optogenetic Control Allows Modeling of Human Neuromuscular Disease
Steinbeck, J. A., Jaiswal, M. K., Calder, E. L., Kishinevsky, S., Weishaupt, A., Toyka, K. V., Goldstein, P. A., & Studer, L. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.10.002 · Cited by 132
Self-citationlet-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis
Patterson, M., Gaeta, X., Loo, K., Edwards, M., Smale, S., Cinkornpumin, J., Xie, Y., Listgarten, J., Azghadi, S., Douglass, S. M., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.08.015 · Cited by 103
Sigl, R., Wandke, C., Rauch, V., Kirk, J. A., Hunt, T., & Geley, S. (2009) · Journal of Cell Science · doi:10.1242/jcs.054197 · Cited by 102
Dysregulation of astrocyte extracellular signaling in Costello syndrome
Krencik, R., Hokanson, K. C., Narayan, A. R., Dvornik, J., Rooney, G. E., Rauen, K. A., Weiss, L. A., Rowitch, D. H., & Ullian, E. M. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa5645 · Cited by 86
Pluripotent stem cell-based disease modeling: current hurdles and future promise
Zeltner, N., & Studer, L. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.10.008 · Cited by 68
Self-citationGarcía‐Campmany, L., & Martı́, E. (2006) · Development · doi:10.1242/dev.02702 · Cited by 60
Cheng, P.-Y., Lin, Y., Chen, Y., Lee, Y., Tai, C.-C., Wang, Y.-T., Chen, Y., Kao, C.-F., & Yu, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022018 · Cited by 59
Ying, S., & Goldstein, P. A. (2005) · Molecular Pain · doi:10.1186/1744-8069-1-2 · Cited by 52
Self-citationMagistri, M., Khoury, N., Mazza, E. M. C., Velmeshev, D., Lee, J. K., Bicciato, S., Tsoulfas, P., & Faghihi, M. A. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13382 · Cited by 46
Roux, P. D. L., & Reh, T. A. (1995) · Journal of Neurobiology · doi:10.1002/neu.480270110 · Cited by 34
Calder, E. L., Tchieu, J. H., Steinbeck, J. A., Tu, E. Y., Keros, S., Ying, S., Jaiswal, M. K., Cornacchia, D., Goldstein, P. A., Tabar, V. S., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3046-14.2015 · Cited by 32
Self-citationHolmqvist, S., Brouwer, M., Djelloul, M., Diaz, A. G., Devine, M. J., Hammarberg, A., Fog, K., Kunath, T., & Roybon, L. (2015) · Stem Cell Research · doi:10.1016/j.scr.2015.05.014 · Cited by 26
Chiricozzi, E., Fernández-Fernández, S., Nardicchi, V., Almeida, Á., Bolaños, J. P., & Goracci, G. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06567.x · Cited by 25
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
