From Human Pluripotent Stem Cells to Cortical Circuits
Abstract
Understanding the development of the human brain in relation with evolution is an important frontier field in developmental biology. In particular, investigating the mechanisms underlying the greatly increased relative size and complexity of the cerebral cortex, the seat of our enhanced cognitive abilities, remains a fascinating yet largely unsolved question. Though many advances in our understanding have been gained from the study of animal models, as well as human genetics and embryology, large gaps remain in our knowledge of the molecular mechanisms that control human cortical development. Interestingly, many aspects of corticogenesis can be recapitulated in vitro from mouse and human embryonic or induced pluripotent stem cells (PSCs), using a variety of experimental systems from 2D models to organoids to xenotransplantation. This has provided the opportunity to study these processes in an accessible and physiologically relevant setting. In this chapter, we will discuss how conserved and divergent features of primate/human corticogenesis can be modeled and studied mechanistically using PSC-based models of corticogenesis. We will also review what has been learned through these approaches about pathological defects of human corticogenesis, from early neurogenesis to late neuronal maturation and connectivity.
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Xenotransplanted neurons reach much more advanced stages of spine maturation than reported so far in in vitro models of human corticogenesis, using adherent cultures or organoids.
“The xenotransplanted neurons also reach much more advanced stages of spine maturation than reported so far in in vitro models of human corticogenesis, using adherent cultures or organoids (Astick and Vanderhaeghen, 2018, Di Lullo and Kriegstein, 2017, Lancaster and Knoblich, 2014)”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Astick and Vanderhaeghen, 2018
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Author response: Human adherent cortical organoids in a multi-well format
van der Kroeg, M., Bansal, S., Unkel, M., Smeenk, H., Kushner, S. A., & de Vrij, F. M. S. (2024) · eLife · doi:10.7554/elife.98340.1.sa4
eLife Assessment: Human adherent cortical organoids in a multi-well format
Konopka, G. (2024) · eLife · doi:10.7554/elife.98340.1.sa3
Human adherent cortical organoids in a multi-well formatPreprint
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Human adherent cortical organoids in a multiwell formatPreprint
van der Kroeg, M., Bansal, S., Unkel, M., Smeenk, H., Kushner, S. A., & de Vrij, F. M. S. (2026) · eLife · doi:10.7554/elife.98340.2
Carpentieri, J. A. (2020) · theses.fr (ABES) · doi:10.70675/1e00c88fzf627z42c5za72ez7da656ac6044
- Authors
- Astick, M., & Vanderhaeghen, P.
- Affiliations
- Université Libre de Bruxelles (BE)
- Corresponding author
- Vanderhaeghen, Pierre
- Venue
- Current Topics in Developmental Biology
- Publisher
- Elsevier
- Published
- 2018
- Volume
- 129
- Pages
- 67-98
- ISSN
- 0070-2153 (ISSN-L)
- OpenAlex
- W2800979286
- Cited by
- 34
- References
- 117
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 12 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 5
- FWCI
- 4.31
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Current topics in developmental biology/Current Topics in Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Waalse Gewest
- Walloon excellence in life sciences and biotechnology
- 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, human brain evolution, human pluripotent stem cells, induced pluripotent stem cells, organoids, xenotransplantation, neurogenesis, neuronal maturation, neuronal connectivity, primate brain development
- MeSH terms
- Animals, Cerebral Cortex, Humans, Mammals, Models, Biological, Nerve Net, Organoids, Pluripotent Stem Cells
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