Cited by 31Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationPluripotent Stem Cells Research

Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates

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Micali, Nicola, Kim, Suel-Kee, Diaz-Bustamante, Marcelo, Stein-O’Brien, Genevieve, Seo, Seungmae, Shin, Joo-Heon, Rash, Brian G., Ma, Shaojie +15 more·2020·Cell Reports

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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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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.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-05
Volume
31
Issue
5
Pages
107599
ISSN
2211-1247 (ISSN-L)
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
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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