2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size
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Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.
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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 [39]
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References 44 · Cited by 353
- Authors
- Otani, T., Marchetto, M. C., Gage, F. H., Simons, B. D., & Livesey, F. J.
- Affiliations
- University of Cambridge (GB)
- Salk Institute for Biological Studies (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Corresponding author
- Livesey, Frederick J.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 18
- Issue
- 4
- Pages
- 467-480
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4826446
- OpenAlex
- W2330595735
- Cited by
- 353
- References
- 44
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 32 · 2023: 35 · 2022: 38 · 2021: 47 · 2020: 35 · 2019: 33 · 2018: 29 · 2017: 30 · 2016: 18 · 2015: 1
- FWCI
- 18.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell stem cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (098357/Z/12/Z)
- Medical Research Council (MR/L023784/2, MC_PC_12009, MR/L023784/1)
- 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
- cortical development, cortical progenitor cells, brain size, non-human primates, pluripotent stem cell differentiation, organoids, progenitor cell proliferation, neurogenesis timing, species differences, cognitive ability
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Humans, Models, Biological, Neurons, Organ Size, Organoids, Primates, Species Specificity, Pluripotent Stem Cells
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