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Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
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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.
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“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
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“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]
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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
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