Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes
Open accessAbstract
Significance: Molecular mechanisms underlying distinct disabilities during neurological diseases may differ based on the neurological pathway involved. Multiple sclerosis (MS) is multifocal, characterized by distinct disabilities affecting walking, vision, cognition, and fatigue. Neuroprotective treatments tailored for each disability may be more effective than nonspecific treatments aiming to reduce a composite of disabilities in clinical trials. Here, we use the MS model to apply a cell-specific and region-specific gene expression approach to discover targets in distinct neuroanatomic regions. Altered cholesterol synthesis gene expression in astrocytes in spinal cord and optic nerve was identified as a potential target for walking and visual disabilities, respectively. This disability-specific discovery approach represents a strategy for finding neuroprotective treatments for multifocal neurodegenerative diseases.
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Transcriptomic 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 [70]
The Results section, “Regional Differences in Astrocyte-Specific Gene Expression During EAE” (page unavailable), reports distinct astrocyte gene-expression patterns across CNS regions during EAE. This paper studies one disease model, so it does not itself establish differences between disease models. The brain-tumor clause is attached to citation 71, not this source. (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 [70]
Transcriptomic studies suggested complex functional changes in reactive astrocytes, including novel regenerative functions, proliferation, neural stem cell potential, and loss of homeostatic functions.
“These studies also suggested complex functional changes in reactive astrocytes, including novel regenerative functions70, proliferation, and neural stem cell potential68, as well as loss of homeostatic functions66.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [70]
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Self-citation
- Authors
- Itoh, N., Itoh, Y., Tassoni, A., Ren, E., Kaito, M., Ohno, A., Ao, Y., Farkhondeh, V., Johnsonbaugh, H., Burda, J., Sofroniew, M. V., & Voskuhl, R. R.
- Affiliations
- University of California, Los Angeles (US)
- Department of Neurobiology, University of California, Los Angeles, CA 90095
- Corresponding author
- Voskuhl, Rhonda R.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-12-26
- Volume
- 115
- Issue
- 2
- Pages
- E302-E309
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5777065
- OpenAlex
- W2777702274
- Cited by
- 253
- References
- 71
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 25 · 2023: 38 · 2022: 37 · 2021: 42 · 2020: 40 · 2019: 27 · 2018: 12
- FWCI
- 16.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Conrad N. Hilton Foundation (20150232)
- Office of Extramural Research, National Institutes of Health (R01NS096748)
- California Community Foundation (BAPP-15-118094)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- multiple sclerosis, experimental autoimmune encephalomyelitis, astrocytes, region-specific gene expression, RiboTag, cholesterol biosynthesis, neuroinflammation, spinal cord, optic nerve, optic chiasm, cerebellum, cerebral cortex, hippocampus, multifocality
- MeSH terms
- Animals, Astrocytes, Cholesterol, Encephalomyelitis, Autoimmune, Experimental, Gene Expression Regulation, Homeostasis, Mice, Inbred C57BL, Multiple Sclerosis, RNA, Messenger, Down-Regulation, Up-Regulation, 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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