The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Open accessAbstract
Current neural induction protocols for human embryonic stem (hES) cells rely on embryoid body formation, stromal feeder co-culture or selective survival conditions. Each strategy has considerable drawbacks, such as poorly defined culture conditions, protracted differentiation and low yield. Here we report that the synergistic action of two inhibitors of SMAD signaling, Noggin and SB431542, is sufficient to induce rapid and complete neural conversion of >80% of hES cells under adherent culture conditions. Temporal fate analysis reveals the appearance of a transient FGF5(+) epiblast-like stage followed by PAX6(+) neural cells competent to form rosettes. Initial cell density determines the ratio of central nervous system and neural crest progeny. Directed differentiation of human induced pluripotent stem (hiPS) cells into midbrain dopamine and spinal motoneurons confirms the robustness and general applicability of the induction protocol. Noggin/SB431542-based neural induction should facilitate the use of hES and hiPS cells in regenerative medicine and disease modeling and obviate the need for protocols based on stromal feeders or embryoid bodies.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Noggin is essential for neural lineage induction via bone morphogenic protein (BMP) antagonism (Chambers et al., 2009).”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Chambers et al., 2009
Experimental — accuracy not yet measuredIn the citing paper
“Commonly, neural induction in brain organoids includes inhibition of SMAD signalling to inhibit mesoderm and endoderm formation, followed by the provision of specific morphogens and fate-specifying molecules18.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [18]
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
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310
Reprogramming of human somatic cells to pluripotency with defined factors
Park, I.-H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W., & Daley, G. Q. (2008) · Nature · doi:10.1038/nature06534 · Cited by 2,436
Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., Reinecke, H., Xu, C., Hassanipour, M., Police, S., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1327 · Cited by 2,235
New cell lines from mouse epiblast share defining features with human embryonic stem cells
Tesar, P. J., Chenoweth, J. G., Brook, F. A., Davies, T. J., Evans, E. P., Mack, D. L., Gardner, R. L., & McKay, R. D. G. (2007) · Nature · doi:10.1038/nature05972 · Cited by 2,187
A ROCK inhibitor permits survival of dissociated human embryonic stem cells
Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S.-I., Muguruma, K., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1310 · Cited by 2,055
Efficient differentiation of human embryonic stem cells to definitive endoderm
D'Amour, K. A., Agulnick, A. D., Eliazer, S., Kelly, O. G., Kroon, E., & Baetge, E. E. (2005) · Nature Biotechnology · doi:10.1038/nbt1163 · Cited by 1,730
Induction of Midbrain Dopaminergic Neurons from ES Cells by Stromal Cell–Derived Inducing Activity
Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S., & Sasai, Y. (2000) · Neuron · doi:10.1016/s0896-6273(00)00083-0 · Cited by 1,277
Smith, W. C., & Harland, R. M. (1992) · Cell · doi:10.1016/0092-8674(92)90316-5 · Cited by 1,184
Xenopus chordin: A novel dorsalizing factor activated by organizer-specific homeobox genes
Sasai, Y. (1994) · Cell · doi:10.1016/0092-8674(94)90068-x · Cited by 1,122
Flagged first, then by citations
Cited by
Sorted by citations
Items 1,001–1,017 of 1,017
Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders
Schadt, E. E., Buchanan, S., Brennand, K. J., & Merchant, K. M. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00252 · Cited by 39
From Human Pluripotent Stem Cells to Cortical Circuits
Astick, M., & Vanderhaeghen, P. (2018) · Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2018.02.011 · Cited by 34
Modeling motor neuron disease: the matter of time
Arbab, M., Baars, S., & Geijsen, N. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.07.008 · Cited by 33
AAV vectors trigger DNA damage responses and STING-dependent inflammation in human CNS cells
Costa-Verdera, H., Meneghini, V., Fitzpatrick, Z., Alezz, M. A., Fabyanic, E., Huang, X., Dzhashiashvili, Y., Ahiya, A., Mangiameli, E., Valeri, E., et al. (2024) · doi:10.21203/rs.3.rs-4171795/v1 · Cited by 32
Costa-Verdera, H., Meneghini, V., Fitzpatrick, Z., Abou Alezz, M., Fabyanic, E., Huang, X., Dzhashiashvili, Y., Ahiya, A., Mangiameli, E., Valeri, E., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58778-3 · Cited by 32
Micali, N., Kim, S.-K., Diaz-Bustamante, M., Stein-O’Brien, G., Seo, S., Shin, J.-H., Rash, B. G., Ma, S., Wang, Y., Olivares, N. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107599 · Cited by 31
Hartmann, J., Henschel, N., Bartmann, K., Dönmez, A., Brockerhoff, G., Koch, K., & Fritsche, E. (2023) · Cells · doi:10.3390/cells12091270 · Cited by 31
Advances in Cerebral Organoid Systems and their Application in Disease Modeling
Liu, F., Huang, J., Zhang, L., Chen, J., Zeng, Y., Tang, Y., & Liu, Z. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.12.013 · Cited by 27
Bartalska, K., Hübschmann, V., Korkut-Demirbaş, M., Cubero, R. J. A., Venturino, A., Rössler, K., Czech, T., & Siegert, S. (2022) · iScience · doi:10.1016/j.isci.2022.104580 · Cited by 22
Nath, S. C., Tokura, T., Kim, M., & Kino‐oka, M. (2018) · Biotechnology and Bioengineering · doi:10.1002/bit.26526 · Cited by 19
Cusulin, C., Wells, I., Badillo, S., Duran-Pacheco, G. C., Baumann, K., & Patsch, C. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.103392 · Cited by 13
Quality criteria for in vitro human pluripotent stem cell-derived models of tissue-based cells
Pistollato, F., Bal-Price, A., Coecke, S., Parvatam, S., Pamies, D., Czysz, K., Hao, J., Kee, K., Teo, A. K. K., Niu, S., et al. (2022) · Reproductive Toxicology · doi:10.1016/j.reprotox.2022.06.003 · Cited by 10
Human iPSC Models in Drug Discovery: Opportunities and Challenges
Silva, M. C., Cross, A., Brandon, N. J., & Haggarty, S. J. (2017) · Comprehensive Medicinal Chemistry III · doi:10.1016/b978-0-12-409547-2.12284-x · Cited by 6
Yoo, M., Choi, D. C., Murphy, A., Ahsan, A. M., & Junn, E. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104709 · Cited by 6
Kang, J., Gong, J., Yang, C., Lin, X., Yan, L., Gong, Y., & Xu, H. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10553-x · Cited by 5
Coulon, A., Rabiller, F., Takalo, M., Roy, A., Pelletier, A., Martiskainen, H., Siedlecki-Wullich, D., Lannette-Weimann, N., Majerníková, N., Grenon, A., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02709-5 · Cited by 1
“In both protocols, iPSCs were induced into neural stem cells through dual SMAD inhibition, where progenitors upregulate PAX6 and EMX1 genes, suggesting a forebrain-like phenotype 54 .”
Spänle, J. V., Haiber, L. M., & Seeger, B. (2026) · Frontiers in Toxicology · doi:10.3389/ftox.2026.1800157 · Cited by 1
Metadata
- Authors
- Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Chambers, Stuart M
- Studer, Lorenz
- Venue
- Nature Biotechnology
- Published
- 2009-03
- Volume
- 27
- Issue
- 3
- Pages
- 275-280
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC2756723
- OpenAlex
- W2087786585
- Cited by
- 3,620
- References
- 24
- Citations by year
- 2026: 155 · 2025: 211 · 2024: 225 · 2023: 241 · 2022: 229 · 2021: 287 · 2020: 292 · 2019: 238 · 2018: 241 · 2017: 235 · 2016: 240 · 2015: 225 · 2014: 185 · 2013: 199 · 2012: 184
- FWCI
- 55.89
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-05-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS052671)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- neuronal differentiation, human embryonic stem cells, induced pluripotent stem cells, noggin, SB431542, epiblast-like cells, Pax6, rosette formation, midbrain dopaminergic neurons, spinal motoneurons, adherent culture
- MeSH terms
- Noggin Protein, Carrier Proteins, Cell Differentiation, Humans, Mesencephalon, Neurons, Signal Transduction, Cell Culture Techniques, Pluripotent Stem Cells, Smad Proteins, Embryonic 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
