Identification of diverse astrocyte populations and their malignant analogs
Open accessAbstract
Astrocytes are the most abundant cell type in the brain, where they perform a wide array of functions, yet the nature of their cellular heterogeneity and how it oversees these diverse roles remains shrouded in mystery. Using an intersectional fluorescence-activated cell sorting-based strategy, we identified five distinct astrocyte subpopulations present across three brain regions that show extensive molecular diversity. Application of this molecular insight toward function revealed that these populations differentially support synaptogenesis between neurons. We identified correlative populations in mouse and human glioma and found that the emergence of specific subpopulations during tumor progression corresponded with the onset of seizures and tumor invasion. In sum, we have identified subpopulations of astrocytes in the adult brain and their correlates in glioma that are endowed with diverse cellular, molecular and functional properties. These populations selectively contribute to synaptogenesis and tumor pathophysiology, providing a blueprint for understanding diverse astrocyte contributions to neurological 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 [69]
The Results (page unavailable) describe astrocyte subpopulations across several brain regions and differing locations within the cortex, supporting spatial diversity among astrocytes. The paper does not identify an “Astro–Epen” class or compare its spatial patterns with those of all other non-neuronal cell types, so it does not support the superlative claim. (LLM, conf=0.82)
Experimental — accuracy not yet measuredTranscriptomic profiling shows that reactive astrocytes adopt distinct molecular states in different disease models, in different CNS regions, and in brain tumors.
“Such transcriptomic profiling specifically shows that reactive astrocytes adopt distinct molecular states in different disease models48,66–70, in different CNS regions70, and in brain tumors71.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [71]
The Results section on malignant glioma reports distinct expression-profile correlations between astrocyte subpopulations and glioblastoma subtypes, and the Discussion describes molecularly distinct populations emerging during tumor progression. This supports the brain-tumor portion attached to this citation, but the paper does not establish that reactive astrocytes adopt those states; it studies astrocyte subpopulations and their malignant glioma analogs. (LLM, conf=0.86)
Experimental — accuracy not yet measuredReactive astrocytes are diverse, as demonstrated by transcriptomic profiling of mouse bulk astrocytes or preselected astrocyte populations.
“Likewise, reactive astrocytes are also diverse, as unequivocally demonstrated by microarray-based66–68 and RNAseq-based48,69–71 transcriptomic profiling of mouse bulk astrocytes48,66–70 or of astrocyte populations preselected according to cell-surface markers71.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [71]
The Results section, “Heterogeneity of Aldh1l1–GFP+ astrocyte subpopulations” (page unavailable), reports RNA-seq profiling of FACS-isolated mouse astrocyte populations and distinct molecular signatures. This supports the marker-preselected-populations part of the citation, but the profiled populations are not identified as reactive astrocytes; the paper therefore does not establish the claim about reactive astrocyte diversity. (LLM, conf=0.87)
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 [26]
The Discussion (page unavailable) says astrocyte diversity in the adult brain remained poorly understood, supporting the general knowledge-gap claim. But the study characterizes adult mouse brain regions, not different cortical areas in the aging human brain; its human evidence is limited to a comparison with human astrocyte gene signatures. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDiversity within astrocyte populations from mouse models may be dissected by combining FACS and cell-surface markers identified in screens.
“Alternatively, the diversity within astrocyte populations from mouse models may be dissected out by combining fluorescence-activated cell sorting (FACS) and cell-surface markers identified in screens71.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [71]
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- Authors
- John Lin, C.-C., Yu, K., Hatcher, A., Huang, T.-W., Lee, H. K., Carlson, J., Weston, M. C., Chen, F., Zhang, Y., Zhu, W., Mohila, C. A., Ahmed, N., Patel, A. J., Arenkiel, B. R., Noebels, J. L., Creighton, C. J., & Deneen, B.
- Affiliations
- Baylor College of Medicine (US)
- University of Vermont (US)
- Corresponding author
- Creighton, Chad J
- Deneen, Benjamin
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2017-02-06
- Volume
- 20
- Issue
- 3
- Pages
- 396-405
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5824716
- OpenAlex
- W2587576402
- Cited by
- 525
- References
- 49
- Citations by year
- 2026: 31 · 2025: 49 · 2024: 53 · 2023: 59 · 2022: 57 · 2021: 80 · 2020: 82 · 2019: 48 · 2018: 38 · 2017: 28
- FWCI
- 26.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Sontag Foundation
- National Institute on Aging (RF1AG054111)
- National Heart, Lung, and Blood Institute (T32HL092332)
- National Cancer Institute (P30CA125123)
- National Institute of General Medical Sciences (R25GM056929, R25GM069234)
- National Institute of Allergy and Infectious Diseases (P30AI036211)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK109934)
- National Institute of Neurological Disorders and Stroke (R21NS089366, R00NS087095, K08NS102474, R01NS071153, R01NS029709)
- National Center for Research Resources (S10RR024574)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083092)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- astrocyte heterogeneity, astrocyte subpopulations, high-grade glioma, synaptogenesis, glioma progression, tumor invasion
- MeSH terms
- Formyltetrahydrofolate Dehydrogenase, Aldehyde Dehydrogenase, Oxidoreductases Acting on CH-NH Group Donors, Animals, Astrocytes, Brain, Female, Flow Cytometry, Glioma, Humans, Male, Mice, Transgenic, Neurons, Seizures, Synapses, Coculture Techniques, Mice, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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