Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence
Open accessAbstract
Astrocytes are ubiquitous in the brain and are widely held to be largely identical. However, this view has not been fully tested, and the possibility that astrocytes are neural circuit specialized remains largely unexplored. Here, we used multiple integrated approaches, including RNA sequencing (RNA-seq), mass spectrometry, electrophysiology, immunohistochemistry, serial block-face-scanning electron microscopy, morphological reconstructions, pharmacogenetics, and diffusible dye, calcium, and glutamate imaging, to directly compare adult striatal and hippocampal astrocytes under identical conditions. We found significant differences in electrophysiological properties, Ca 2+ signaling, morphology, and astrocyte-synapse proximity between striatal and hippocampal astrocytes. Unbiased evaluation of actively translated RNA and proteomic data confirmed significant astrocyte diversity between hippocampal and striatal circuits. We thus report core astrocyte properties, reveal evidence for specialized astrocytes within neural circuits, and provide new, integrated database resources and approaches to explore astrocyte diversity and function throughout the adult brain. VIDEO ABSTRACT.
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Less 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 [27]
The Introduction says astrocyte diversity remains incompletely tested, while noting emerging evidence in aging and disease. The Results examine transcriptomic differences between the striatum and hippocampus of adult mice; the paper does not establish the specific knowledge gap concerning different cortical areas in the aging human brain. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAstrocytes in the healthy brain are diverse and specialized to perform specific roles in distinct CNS circuits.
“Transcriptomics has contributed to a fundamental discovery: astrocytes in the healthy brain are diverse and specialized to perform specific roles in distinct CNS circuits14,65.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [65]
Heterogeneity exists between astrocytes from different brain areas.
“which is particularly important because heterogeneity exists between astrocytes from different brain areas (Chai et al., 2017).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Chai et al., 2017
Adult astrocyte gene expression datasets are in broad agreement with other microarray and RNA-seq profiles of astrocytes from the developing and adult brain.
“Our adult astrocyte gene expression datasets are in broad agreement with other microarray and RNA-seq profiles of astrocytes from the developing and adult brain (Cahoy et al., 2008; Chai et al., 2017; Doyle et al., 2008; Morel et al., 2017; Zhang et al., 2014).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Chai et al., 2017
Ribo-tag restricts analysis to ribosome-associated mRNAs, which are more likely to be actively being made into proteins, providing a representation of the translational state of the cells.
“Ribo-tag restricts analysis to ribosome-associated mRNAs, which are more likely to be actively being made into proteins, providing a representation of the translational state of the cells, a similar approach to that used by others (Chai et al., 2017; Doyle et al., 2008; Morel et al., 2017).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Chai et al., 2017
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References 63 · Cited by 769
- Authors
- Chai, H., Diaz-Castro, B., Shigetomi, E., Monte, E., Octeau, J. C., Yu, X., Cohn, W., Rajendran, P. S., Vondriska, T. M., Whitelegge, J. P., Coppola, G., & Khakh, B. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Khakh, Baljit S.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 95
- Issue
- 3
- Pages
- 531-549.e9
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5811312
- OpenAlex
- W2735769265
- Cited by
- 769
- References
- 63
- Citations by year
- 2026: 57 · 2025: 82 · 2024: 110 · 2023: 108 · 2022: 81 · 2021: 113 · 2020: 89 · 2019: 50 · 2018: 68 · 2017: 11
- FWCI
- 29.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (MH099559, MH104069, MH106197)
- NINDS
- UCLA (P30 NS062691)
- JSPS KAKENHI (JP15KK0340)
- American Heart Association (13PRE14430015)
- UCSD/UCLA NIDDK (P30 DK063491)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- astrocyte heterogeneity, striatal astrocytes, hippocampal astrocytes, astrocyte signaling, astrocyte morphology, transcriptome, proteome
- MeSH terms
- Animals, Astrocytes, Calcium, Corpus Striatum, Hippocampus, Synapses, Neostriatum, Glutamic Acid, Calcium Signaling, Proteomics, Mice, Transcriptome
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