Fate mapping of neural stem cell niches reveals distinct origins of human cortical astrocytes
Open accessAbstract
Progenitors of the developing human neocortex reside in the ventricular and outer subventricular zones (VZ and OSVZ, respectively). However, whether cells derived from these niches have similar developmental fates is unknown. By performing fate mapping in primary human tissue, we demonstrate that astrocytes derived from these niches populate anatomically distinct layers. Cortical plate astrocytes emerge from VZ progenitors and proliferate locally, while putative white matter astrocytes are morphologically heterogeneous and emerge from both VZ and OSVZ progenitors. Furthermore, via single-cell sequencing of morphologically defined astrocyte subtypes using Patch-seq, we identify molecular distinctions between VZ-derived cortical plate astrocytes and OSVZ-derived white matter astrocytes that persist into adulthood. Together, our study highlights a complex role for cell lineage in the diversification of human neocortical astrocytes.
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White matter fibrous astrocytes are markedly different from protoplasmic cortical astrocytes.
“white matter fibrous astrocytes are markedly different from protoplasmic cortical astrocytes40,41”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [41]
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- Authors
- Allen, D. E., Donohue, K. C., Cadwell, C. R., Shin, D., Keefe, M. G., Sohal, V. S., & Nowakowski, T. J.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Nowakowski, Tomasz J.
- ORCID
- Venue
- Science
- Published
- 2022-06-24
- Volume
- 376
- Issue
- 6600
- Pages
- 1441-1446
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9233096
- OpenAlex
- W4280643668
- Cited by
- 67
- References
- 7
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 18 · 2023: 18 · 2022: 7
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Simons Foundation Autism Research Initiative (SFARI 491371)
- National Institutes of Health (NS070680)
- University of California, San Francisco
- National Institute of Mental Health (RF1MH121268, U01MH115747)
- National Cancer Institute (P50CA097257)
- National Institute of Neurological Disorders and Stroke (R25NS070680, P01NS083513, K08NS126573, R01NS123263)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007470)
- 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 › Single-cell and spatial transcriptomics
- Keywords
- cortical astrocytes, ventricular zone, outer subventricular zone, human neocortex development, fate mapping, white matter astrocytes, astrocyte subtypes, Patch-seq, cell lineage, astrocyte heterogeneity
- MeSH terms
- Astrocytes, Humans, Cell Lineage, Neocortex, Stem Cell Niche, Neurogenesis, Neural Stem Cells, Primary Cell Culture
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