Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell–derived neocortex
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Significance: Using 3D culture of human ES cells, we show new self-organizing aspects of human corticogenesis: spontaneous development of intracortical polarity, curving morphology, and complex zone separations. Moreover, this culture generates species-specific progenitors, outer radial glia, which are abundantly present in the human, but not mouse, neocortex. Our study suggests an unexpectedly wide range of self-organizing events that are driven by internal programs in human neocortex development.
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Production of radial glial cells, intermediate progenitors, and deep- and superficial-layer neurons in an ordered temporal fashion has been reported by studies using all current protocols.
“The production of radial glial cells, intermediate progenitors, and deep- and superficial-layer neurons in an ordered temporal fashion has been reported by studies using all of the protocols currently in use2,3,5,25.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [3]
These protocols generated organoids with a dorsalized neuroepithelium that reproduced certain structural and cell-behaviour aspects of cortical development.
“Both of these protocols generated organoids containing a dorsalized neuroepithelium that reproduced certain aspects of cortical development, both structurally and in terms of cell behaviour.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [3]
The developmental timing of cortical neurogenesis appears conserved in vitro and has been demonstrated with both suspension and adherent differentiation methods.
“Interestingly, the developmental timing of cortical neurogenesis appears to be conserved in vitro and has been demonstrated with both suspension and adherent differentiation methods2,3,5,39.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [3]
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- Authors
- Kadoshima, T., Sakaguchi, H., Nakano, T., Soen, M., Ando, S., Eiraku, M., & Sasai, Y.
- Affiliations
- Kyoto University (JP)
- Laboratory of Organogenesis and Neurogenesis and
- RIKEN (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-11-25
- Volume
- 110
- Issue
- 50
- Pages
- 20284-20289
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3864329
- OpenAlex
- W2051785391
- Cited by
- 999
- References
- 33
- Citations by year
- 2026: 62 · 2025: 99 · 2024: 90 · 2023: 84 · 2022: 122 · 2021: 113 · 2020: 113 · 2019: 94 · 2018: 66 · 2017: 66 · 2016: 44 · 2015: 30 · 2014: 16
- FWCI
- 11.13
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-04-29)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (24680037)
- Japan Science and Technology Agency
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- human embryonic stem cells, self-organization, axial polarity, subplate, cortical plate, outer subventricular zone, outer radial glia, 3D cell culture, cortical morphogenesis
- MeSH terms
- Amides, Collagen, Drug Combinations, Humans, Laminin, Neuroglia, Proteoglycans, Pyridines, Species Specificity, Cell Polarity, Cell Culture Techniques, Neocortex, Organogenesis, Embryonic Stem Cells
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