The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
CNS fibroblasts form a fibrotic scar in response to immune cell infiltration.
Open accessAbstract
Fibrosis is a common pathological response to inflammation in many peripheral tissues and can prevent tissue regeneration and repair. Here, we identified persistent fibrotic scarring in the CNS following immune cell infiltration in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Using lineage tracing and single-cell sequencing in EAE, we determined that the majority of the fibrotic scar is derived from proliferative CNS fibroblasts, not pericytes or infiltrating bone marrow-derived cells. Ablating proliferating fibrotic cells using cell-specific expression of herpes thymidine kinase led to an increase in oligodendrocyte lineage cells within the inflammatory lesions and a reduction in motor disability. We further identified that interferon-gamma pathway genes are enriched in CNS fibrotic cells, and the fibrotic cell-specific deletion of Ifngr1 resulted in reduced fibrotic scarring in EAE. These data delineate a framework for understanding the CNS fibrotic response.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, recent studies implicate activation of perivascular fibroblasts as a contributing factor to neurodegeneration at early stages of Amyotrophic Lateral Sclerosis,20 and meningeal fibroblasts-induced fibrotic scarring has been highlighted as a potential player in the pathogenesis of multiple sclerosis.21”
From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [21]
Experimental — accuracy not yet measuredIn the citing paper
“a scRNAseq analysis showed that fibroblasts from EAE lesions upregulate interferon γ (IFNγ) signaling, and conditional deletion of IFN receptor γ from fibroblasts partially blocked fibroblast expansion”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Dorrier et al., 2021
In the citing paper
“Using a Col1a1-GFP mouse line in conjunction with an EAE model, two independent groups identified substantial increases in fibroblasts within spinal cord lesion sites”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Dorrier et al., 2021
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Aran, D., Looney, A. P., Liu, L., Wu, E., Fong, V., Hsu, A., Chak, S., Naikawadi, R. P., Wolters, P. J., Abate, A. R., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0276-y · Cited by 4,984
Self-citationBataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958
Cellular and molecular mechanisms of fibrosis
Wynn, T. (2008) · The Journal of Pathology · doi:10.1002/path.2277 · Cited by 4,495
Hafemeister, C., & Satija, R. (2019) · Genome Biology · doi:10.1186/s13059-019-1874-1 · Cited by 4,479
Interferon-γ: an overview of signals, mechanisms and functions
Schroder, K., Hertzog, P. J., Ravasi, T., & Hume, D. A. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0603252 · Cited by 4,120
Lederer, D. J., & Martinez, F. J. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1705751 · Cited by 2,056
A molecular atlas of cell types and zonation in the brain vasculature
Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., et al. (2018) · Nature · doi:10.1038/nature25739 · Cited by 1,892
The Immunological Genome Project: networks of gene expression in immune cells
The Immunological Genome Project Consortium, Heng, T. S. P., Painter, M. W., Elpek, K., Lukacs-Kornek, V., Mauermann, N., Turley, S. J., Koller, D., Kim, F. S., Wagers, A. J., et al. (2008) · Nature Immunology · doi:10.1038/ni1008-1091 · Cited by 1,864
The JAK/STAT signaling pathway
Rawlings, J. S., Rosler, K. M., & Harrison, D. A. (2004) · Journal of Cell Science · doi:10.1242/jcs.00963 · Cited by 1,858
Cited by
Sorted by citations
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797
Revisiting the neurovascular unit
Schaeffer, S. M., & Iadecola, C. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00904-7 · Cited by 699
Astrocytes in human central nervous system diseases: a frontier for new therapies
Verkhratsky, A., Butt, A., Li, B., Illes, P., Zorec, R., Semyanov, A., Tang, Y., & Sofroniew, M. V. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01628-9 · Cited by 428
Single-cell dissection of the human brain vasculature
García, F., Sun, N., Lee, H., Godlewski, B. R., Mathys, H., Galani, K., Zhou, B., Jiang, X., Ng, A. P., Mantero, J. C., et al. (2022) · Nature · doi:10.1038/s41586-022-04521-7 · Cited by 313
Identification, discrimination and heterogeneity of fibroblasts
Lendahl, U., Muhl, L., & Betsholtz, C. (2022) · Nature Communications · doi:10.1038/s41467-022-30633-9 · Cited by 256
Metadata
- Authors
- Dorrier, C. E., Aran, D., Haenelt, E. A., Sheehy, R. N., Hoi, K. K., Pintarić, L., Chen, Y., Lizama, C. O., Cautivo, K. M., Weiner, G. A., Popko, B., Fancy, S. P. J., Arnold, T. D., & Daneman, R.
- Affiliations
- University of California San Diego (US)
- Technion – Israel Institute of Technology (IL)
- University of California, San Francisco (US)
- Northwestern University (US)
- Corresponding author
- Arnold, Thomas D.
- Daneman, Richard
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2021-02
- Volume
- 24
- Issue
- 2
- Pages
- 234-244
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC7877789
- OpenAlex
- W3128620467
- Cited by
- 199
- References
- 58
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 39 · 2023: 44 · 2022: 33 · 2021: 25
- FWCI
- 23.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NS108651-01A1, NS034939, 5K08NS096192-02)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (GM007752)
- National Multiple Sclerosis Society
- UCSF Program for Breakthrough Biomedical Science
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- fibrotic scar, multiple sclerosis, experimental autoimmune encephalomyelitis, immune cell infiltration, fibroblast proliferation, meningeal fibrosis, oligodendrocyte lineage, interferon-gamma, IFNGR1, motor impairment, neuroinflammation
- MeSH terms
- Animals, Blood-Brain Barrier, Encephalomyelitis, Autoimmune, Experimental, Fibroblasts, Fibrosis, Oligodendroglia, Spinal Cord, Neutrophil Infiltration, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review
