The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Notch signalling drives synovial fibroblast identity and arthritis pathology
Open accessAbstract
The synovium is a mesenchymal tissue composed mainly of fibroblasts, with a lining and sublining that surround the joints. In rheumatoid arthritis the synovial tissue undergoes marked hyperplasia, becomes inflamed and invasive, and destroys the joint1,2. It has recently been shown that a subset of fibroblasts in the sublining undergoes a major expansion in rheumatoid arthritis that is linked to disease activity3–5; however, the molecular mechanism by which these fibroblasts differentiate and expand is unknown. Here we identify a critical role for NOTCH3 signalling in the differentiation of perivascular and sublining fibroblasts that express CD90 (encoded by THY1). Using single-cell RNA sequencing and synovial tissue organoids, we found that NOTCH3 signalling drives both transcriptional and spatial gradients—emanating from vascular endothelial cells outwards—in fibroblasts. In active rheumatoid arthritis, NOTCH3 and Notch target genes are markedly upregulated in synovial fibroblasts. In mice, the genetic deletion of Notch3 or the blockade of NOTCH3 signalling attenuates inflammation and prevents joint damage in inflammatory arthritis. Our results indicate that synovial fibroblasts exhibit a positional identity that is regulated by endothelium-derived Notch signalling, and that this stromal crosstalk pathway underlies inflammation and pathology in inflammatory arthritis. NOTCH3 signalling is shown to be the underlying driver of the differentiation and expansion of a subset of synovial fibroblasts implicated in the pathogenesis of rheumatoid arthritis.
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Traag, V. A., Waltman, L., & van Eck, N. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-41695-z · Cited by 5,635
The Pathogenesis of Rheumatoid Arthritis
McInnes, I. B., & Schett, G. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1004965 · Cited by 5,514
Reversed graph embedding resolves complex single-cell trajectories
Qiu, X., Mao, Q., Tang, Y., Wang, L., Chawla, R., Pliner, H. A., & Trapnell, C. (2017) · Nature Methods · doi:10.1038/nmeth.4402 · Cited by 5,070
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137
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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
SoupX removes ambient RNA contamination from droplet based single-cell RNA sequencing data
Young, M. D., & Behjati, S. (2018) · doi:10.1101/303727 · Cited by 1,648
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Young, M. D., & Behjati, S. (2020) · GigaScience · doi:10.1093/gigascience/giaa151 · Cited by 1,619
Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Zhang, F., Wei, K., Slowikowski, K., Fonseka, C. Y., Rao, D. A., Kelly, S., Goodman, S. M., Tabechian, D., Hughes, L. B., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0378-1 · Cited by 1,367
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Metadata
- Authors
- Wei, K., Korsunsky, I., Marshall, J. L., Gao, A., Watts, G. F. M., Major, T., Croft, A. P., Watts, J., Blazar, P. E., Lange, J. K., Thornhill, T. S., Filer, A., Raza, K., Donlin, L. T., Accelerating Medicines Partnership Rheumatoid Arthritis & Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Albrecht, J., Anolik, J. H., Apruzzese, W., Boyce, B. F., Boyle, D. L., Bridges, S. L., Buckner, J. H., Bykerk, V. P., DiCarlo, E., Dolan, J., Eisenhaure, T. M., Firestein, G. S., Fonseka, C. Y., Goodman, S. M., Gravallese, E. M., Gregersen, P. K., Guthridge, J. M., Gutierrez-Arcelus, M., Hacohen, N., Holers, V. M., Hughes, L. B., Ivashkiv, L. B., James, E. A., James, J. A., Jonsson, A. H., Keegan, J., Kelly, S., Lee, Y. C., Lederer, J. A., Lieb, D. J., Mandelin, A. M., McGeachy, M. J., McNamara, M. A., Mears, J. R., Meednu, N., Mizoguchi, F., Moreland, L., Nguyen, J. P., Nusbaum, C., Noma, A., Orange, D. E., Perlman, H., Pitzalis, C., Rangel-Moreno, J., Rao, D. A., Rohani-Pichavant, M., Ritchlin, C., Robinson, W. H., Salomon-Escoto, K., Seshadri, A., Seifert, J., Slowikowski, K., Sutherby, D., Tabechian, D., Turner, J. D., Utz, P. J., Zhang, F., Siebel, C. W., Buckley, C. D., Raychaudhuri, S., & Brenner, M. B.
- Venue
- Nature
- Published
- 2020-04-22
- Volume
- 582
- Issue
- 7811
- Pages
- 259-264
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3018856393
- Cited by
- 528
- References
- 43
- FWCI
- 41.47
- Type
- journal article
- Language
- en
- Open access
- green
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- Wei, K., Korsunsky, I., Marshall, J. L., Gao, A., Watts, G. F. M., Major, T., Croft, A. P., Watts, J., Blazar, P. E., Lange, J. K., Thornhill, T. S., Filer, A., Raza, K., Donlin, L. T., Accelerating Medicines Partnership Rheumatoid Arthritis & Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Albrecht, J., Anolik, J. H., Apruzzese, W., Boyce, B. F., . . . Brenner, M. B. (2020). Notch signalling drives synovial fibroblast identity and arthritis pathology. Nature. https://doi.org/10.1038/s41586-020-2222-z
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