Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
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Abstract
Better understanding of the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here, we use RNA sequencing, cell imaging, and lineage tracing of mouse and human in vitro NSCs and monkey brain sections to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs develop from pluripotency in vitro, they transition through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines vary in these early patterning states, leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analyses of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon.
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Variation in the state of hiPS cell lines can lead to divergent neuronal biases.
“Variation in the state of hiPS cell lines can lead to divergent neuronal biases”
From Generation of Functional Human 3D Cortico-Motor Assembloids (2020) · cites this paper as Micali et al., 2020
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Generation of Functional Human 3D Cortico-Motor Assembloids
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- Authors
- Micali, N., Kim, S.-K., Diaz-Bustamante, M., Stein-O’Brien, G., Seo, S., Shin, J.-H., Rash, B. G., Ma, S., Wang, Y., Olivares, N. A., Arellano, J. I., Maynard, K. R., Fertig, E. J., Cross, A. J., Bürli, R. W., Brandon, N. J., Weinberger, D. R., Chenoweth, J. G., Hoeppner, D. J., Sestan, N., Rakic, P., Colantuoni, C., & McKay, R. D.
- Affiliations
- Yale University (US)
- Lieber Institute for Brain Development (US)
- Johns Hopkins University (US)
- AstraZeneca (United States) (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Micali, Nicola
- Rakic, Pasko
- Colantuoni, Carlo
- McKay, Ronald D.
- ORCID
- Micali, Nicola
- Kim, Suel-Kee
- Diaz-Bustamante, Marcelo
- Stein-O’Brien, Genevieve
- Seo, Seungmae
- Shin, Joo-Heon
- Rash, Brian G.
- Ma, Shaojie
- Wang, Yanhong
- Arellano, Jon I.
- Maynard, Kristen R.
- Fertig, Elana J.
- Cross, Alan J.
- Bürli, Roland W.
- Brandon, Nicholas J.
- Weinberger, Daniel R.
- Hoeppner, Daniel J.
- Rakic, Pasko
- Colantuoni, Carlo
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 31
- Issue
- 5
- Pages
- 107599
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7357345
- OpenAlex
- W3021606299
- Cited by
- 31
- References
- 127
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 2
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- AstraZeneca
- National Institutes of Health
- Lieber Institute for Brain Development
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- neural stem cells, cortical excitatory neurons, inhibitory interneurons, glutamatergic neurons, telencephalic development, neuronal fate specification, neurogenesis, pluripotent stem cells, dorsoventral patterning, lineage tracing, RNA sequencing, neuropsychiatric disorders
- MeSH terms
- Cell Differentiation, Cells, Cultured, Humans, Neurons, Signal Transduction, Embryonic Stem Cells, Neurogenesis, Induced Pluripotent Stem Cells, Neural Stem Cells
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