Molecular basis of astrocyte diversity and morphology across the CNS in health and disease
Open accessAbstract
Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity. We identified gene networks correlated with astrocyte morphology, several of which unexpectedly contained Alzheimer’s disease (AD) risk genes. CRISPR/Cas9–mediated reduction of candidate genes reduced astrocyte morphological complexity and resulted in cognitive deficits. The same genes were down-regulated in human AD, in an AD mouse model that displayed reduced astrocyte morphology, and in other human brain disorders. We thus provide comprehensive molecular data on astrocyte diversity and mechanisms across the CNS and on the molecular basis of astrocyte morphology in health and disease.
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Of all non-neuronal cell types, the Astro-Epen class exhibits the most diverse spatial patterns.
“Of all the non-neuronal cell types, the Astro–Epen class exhibits the most diverse spatial patterns68,69.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [68]
The Results section, “Region-specific astrocyte genes and pathways” (page unavailable), documents differences among astrocytes across CNS regions. It does not identify an Astro–Epen class or compare its spatial patterns with those of all other non-neuronal cell types, so the claim that it is the most diverse is unsupported. (LLM, conf=0.84)
Experimental — accuracy not yet measuredLess is known about the transcriptomic heterogeneity of astrocytes across different cortical areas in the aging human brain.
“but less is known about the transcriptomic heterogeneity of astrocytes across different cortical areas in the aging human brain.”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [8]
The Strategy and Bioinformatic evaluation of astrocyte diversity sections describe transcriptomic comparisons across adult mouse CNS regions, including cortical areas. Our copy does not state whether transcriptomic heterogeneity across cortical areas in the aging human brain is less well understood; searches for human aging and cortical heterogeneity found no passage addressing that knowledge gap. (LLM, conf=0.75)
Experimental — accuracy not yet measured
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- Authors
- Endo, F., Kasai, A., Soto, J. S., Yu, X., Qu, Z., Hashimoto, H., Gradinaru, V., Kawaguchi, R., & Khakh, B. S.
- Affiliations
- University of California, Los Angeles (US)
- The University of Osaka (JP)
- California Institute of Technology (US)
- Institute for Open and Transdisciplinary Research Initiatives (JP)
- Corresponding author
- Khakh, Baljit S.
- ORCID
- Venue
- Science
- Published
- 2022-11-04
- Volume
- 378
- Issue
- 6619
- Pages
- eadc9020-eadc9020
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9873482
- OpenAlex
- W4308451957
- Cited by
- 560
- References
- 61
- Citations by year
- 2026: 131 · 2025: 189 · 2024: 150 · 2023: 87 · 2022: 3
- FWCI
- 37.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (18H05416, 20H00492)
- National Institute on Aging (R01AG075955)
- National Institute on Drug Abuse (R01DA047444)
- National Institute of Neurological Disorders and Stroke (R35NS111583)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD103557)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- astrocytes, astrocyte morphology, central nervous system, regional gene expression, gene networks, Alzheimer's disease, Alzheimer's disease risk genes, cognitive impairment, brain disorders
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Central Nervous System, Disease Models, Animal, Humans, Mice, Transcriptome
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