Defining the molecular identity and morphology of glia limitans superficialis astrocytes in mouse and human
Open accessPreprint — published as 10.1016/j.celrep.2025.115344
Abstract
Astrocytes are a highly abundant glial cell type that perform critical homeostatic functions in the central nervous system. Like neurons, astrocytes have many discrete heterogenous subtypes. The subtype identity and functions are, at least in part, associated with their anatomical location and can be highly restricted to strategically important anatomical domains. Here, we report that astrocytes forming the glia limitans superficialis , the outermost border of brain and spinal cord, are a highly specialized astrocyte subtype and can be identified by a single marker: Myocilin (Myoc). We show that Myoc + astrocytes cover the entire brain and spinal cord surface, exhibit an atypical morphology, and are evolutionarily conserved from rodents to humans. Identification of this highly specialized astrocyte subtype will advance our understanding of CNS homeostasis and potentially be targeted for therapeutic intervention to combat peripheral inflammatory effects on the CNS.
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ILAs specifically express higher levels of Myoc gene compared to astrocytes residing in other cortical layers, in both mice and humans.
“A recent preprint showed that they specifically express higher levels of Myoc gene compared to astrocytes residing in other cortical layers, in both mice and humans (Hasel et al., 2023).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Hasel et al., 2023
The Results sections on mouse GLS astrocytes and human MYOC+ astrocytes show that Myoc/MYOC is concentrated in surface astrocytes rather than deeper cortical astrocytes. However, the human Results section says these cells only “potentially represent” previously described interlaminar astrocytes; the paper does not establish the claim specifically for ILAs in both species. No page numbers are available in our copy. (LLM, conf=0.86)
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Astrocytes connect specific brain regions through plastic gap junctional networksPreprint
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Self-citationIdentification of Differentially Expressed Genes in Spinal Cord Injury
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Skull–meninges–brain connectivity and extra-axial brain tumours
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The multiple scales of astrocytic functional units
Oliveira, J. F., Agarwal, A., Beckervordersandforth, R., Curreli, S., Denizot, A., Dulla, C. G., Enger, R., Goda, Y., Goshen, I., Holt, M. G., et al. (2026) · Nature Neuroscience · doi:10.1038/s41593-026-02308-x · Cited by 3 · see citing works
Localized mRNAs and protein synthesis in cortical layer 1
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Innate immune signaling and functions in astrocytes
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Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting
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Neuroinflammation in glaucoma: a myriad of cellular pathways and players
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Recent findings on the heterogeneity of astrocytes
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Astrocytic Accumulation at the Choroid Plexus Attachment Region
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Morphological Hallmarks of White Matter Astrocytes Across DevelopmentPreprint
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- Authors
- Hasel, P., Cooper, M. L., Marchildon, A. E., Rufen-Blanchette, U. A., Kim, R. D., Ma, T. C., Kang, U. J., Chao, M. V., & Liddelow, S. A.
- Affiliations
- UK Dementia Research Institute (GB)
- New York University (US)
- NYU Langone Health (US)
- Corresponding author
- Hasel, Philip
- Liddelow, Shane A
- ORCID
- Venue
- Cell Reports
- Publisher
- openRxiv
- Published
- 2023-04-06
- Volume
- 44
- Issue
- 3
- Pages
- 115344-115344
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC10104130
- OpenAlex
- W4407780825
- Cited by
- 47
- References
- 61
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 9 · 2023: 2
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Cell Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Alzheimer's Association (DP2NS117177, NS107616, MH119136)
- Columbia University
- Leon Levy Foundation
- Cure Alzheimer's Fund
- Wellcome Trust (227287/Z/23/Z)
- UK Dementia Research Institute (UK DRI- CF2023)
- National Institutes of Health (1dp2ns117177-01, 1k99ns139313-01a1)
- University of Texas MD Anderson Cancer Center
- Hopkins Population Center, Johns Hopkins University
- Medical Research Council
- National Institute of Mental Health (R01MH119136, R01MH125956)
- National Eye Institute (R01EY033353)
- National Institute of Neurological Disorders and Stroke (DP2NS117177, U19NS107616)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- astrocytes, astrocyte subtypes, myocilin, astrocyte morphology, evolutionary conservation, zebrafish, rodents, non-human primates, CNS homeostasis, peripheral inflammation, blood-brain barrier
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