Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses
Open accessAbstract
Efforts to study the development and function of the human cerebral cortex in health and disease have been limited by the availability of model systems. Extrapolating from our understanding of rodent cortical development, we have developed a robust, multistep process for human cortical development from pluripotent stem cells: directed differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells to cortical stem and progenitor cells, followed by an extended period of cortical neurogenesis, neuronal terminal differentiation to acquire mature electrophysiological properties, and functional excitatory synaptic network formation. We found that induction of cortical neuroepithelial stem cells from human ES cells and human iPS cells was dependent on retinoid signaling. Furthermore, human ES cell and iPS cell differentiation to cerebral cortex recapitulated in vivo development to generate all classes of cortical projection neurons in a fixed temporal order. This system enables functional studies of human cerebral cortex development and the generation of individual-specific cortical networks ex vivo for disease modeling and therapeutic purposes.
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Prolonged maturation was also observed in human neurons obtained using an alternative protocol of in vitro corticogenesis (Shi et al., 2012).
“Prolonged maturation was also observed in human neurons obtained using an alternative protocol of in vitro corticogenesis (Shi et al., 2012)”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Shi et al., 2012
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- Authors
- Shi, Y., Kirwan, P., Smith, J., Robinson, H. P. C., & Livesey, F. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Livesey, Frederick J
- Venue
- Nature Neuroscience
- Published
- 2012-02-05
- Volume
- 15
- Issue
- 3
- Pages
- 477-486
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3882590
- OpenAlex
- W2023652080
- Cited by
- 813
- References
- 13
- Citations by year
- 2026: 27 · 2025: 39 · 2024: 43 · 2023: 56 · 2022: 48 · 2021: 56 · 2020: 67 · 2019: 81 · 2018: 85 · 2017: 65 · 2016: 56 · 2015: 71 · 2014: 45 · 2013: 48 · 2012: 26
- FWCI
- 24.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (079249, 086806, 092096)
- Cancer Research UK
- Biotechnology and Biological Sciences Research Council
- 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
- induced pluripotent stem cells, human embryonic stem cells, cortical progenitor cells, projection neurons, excitatory synapses, retinoid signaling, cortical neurogenesis, disease modeling
- MeSH terms
- Disks Large Homolog 4 Protein, Cell Differentiation, Cell Line, Cells, Cultured, Cerebral Cortex, Fetus, Humans, Membrane Proteins, Nerve Tissue Proteins, Piperidines, Retinoids, RNA, Messenger, Synapses, Tetrodotoxin, Time Factors, Transcription Factors, Signal Transduction, Patch-Clamp Techniques, Gene Expression Regulation, Developmental, Excitatory Amino Acid Antagonists, Glutamic Acid, 6-Cyano-7-nitroquinoxaline-2,3-dione, Ki-67 Antigen, Potassium Channel Blockers, Sodium Channel Blockers, Pluripotent Stem Cells, Intracellular Signaling Peptides and Proteins, Embryonic Stem Cells, Synaptic Potentials, Neurogenesis
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 ›
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