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| DOI | 10.1038/s41586-020-2222-z |
| Notch signalling drives synovial fibroblast identity and arthritis pathology | |
| Han, Xiaoping1,2; Zhou, Ziming1; Fei, Lijiang1; Sun, Huiyu1; Wang, Renying1; Chen, Yao3; Chen, Haide1,4; Wang, Jingjing1,4; Tang, Huanna5; Ge, Wenhao6; Zhou, Yincong7; Ye, Fang1; Jiang, Mengmeng1; Wu, Junqing1; Xiao, Yanyu1; Jia, Xiaoning8; Zhang, Tingyue1; Ma, Xiaojie9; Zhang, Qi10; Bai, Xueli10; Lai, Shujing1; Yu, Chengxuan1; Zhu, Lijun6; Lin, Rui11; Gao, Yuchi12; Wang, Min13; Wu, Yiqing3; Zhang, Jianming14; Zhan, Renya15; Zhu, Saiyong9; Hu, Hailan8; Wang, Changchun16; Chen, Ming7; Huang, He2,17,18; Liang, Tingbo10; Chen, Jianghua5; Wang, Weilin6; Zhang, Dan3; Guo, Guoji1,2,4,17,18 | |
| 2020-03-25 | |
| 发表期刊 | NATURE
 |
| ISSN | 0028-0836 |
| EISSN | 1476-4687 |
| 出版年 | 2020 |
| 卷号 | 582期号:7811页码:259-+ |
| 文章类型 | Article |
| 语种 | 英语 |
| 国家 | USA; England |
| 英文关键词 | 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. 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 joint(1,2). 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 activity(3-5) 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. |
| 领域 | 地球科学 ; 气候变化 ; 资源环境 |
| 收录类别 | SCI-E |
| WOS记录号 | WOS:000528161900001 |
| WOS关键词 | RNA-SEQ ; CELLS ; ARCHITECTURE ; CADHERIN-11 ; EXPRESSION ; PROMOTES ; LOOP |
| WOS类目 | Multidisciplinary Sciences |
| WOS研究方向 | Science & Technology - Other Topics |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281143 |
| 专题 | 地球科学 资源环境科学 气候变化 |
| 作者单位 | 1.Zhejiang Univ, Ctr Stem Cell & Regenerat Med, Sch Med, Hangzhou, Peoples R China; 2.Zhejiang Univ, Affiliated Hosp 1, Bone Marrow Transplantat Ctr, Sch Med, Hangzhou, Peoples R China; 3.Zhejiang Univ, Womens Hosp, Sch Med, Dept Reprod Endocrinol, Hangzhou, Peoples R China; 4.Dr Li Dak Sum & Yip Yio Chin Ctr Stem Cell & Rege, Zhejiang Prov Key Lab Tissue Engn & Regenerat Med, Hangzhou, Peoples R China; 5.Zhejiang Univ, Affiliated Hosp 1, Kidney Dis Ctr, Sch Med, Hangzhou, Peoples R China; 6.Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Hepatobiliary & Pancreat Surg, Hangzhou, Peoples R China; 7.Zhejiang Univ, Coll Life Sci, Hangzhou, Peoples R China; 8.Zhejiang Univ, Ctr Neurosci, Sch Med, Hangzhou, Peoples R China; 9.Zhejiang Univ, Life Sci Inst, Hangzhou, Peoples R China; 10.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Hepatobiliary & Pancreat Surg, Hangzhou, Peoples R China; 11.Hangzhou Repugene Technol, Hangzhou, Peoples R China; 12.Annoroad Gene Technol, Beijing, Peoples R China; 13.Veritas Genet Asia, Hangzhou, Peoples R China; 14.Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Neurosurg, Hangzhou, Peoples R China; 15.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Neurosurg, Hangzhou, Peoples R China; 16.Univ Chinese Acad Sci, Inst Canc Res & Basic Med Sci, Zhejiang Canc Hosp, Chinese Acad Sci,Canc Hosp, Hangzhou, Peoples R China; 17.Zhejiang Univ, Inst Hematol, Hangzhou, Peoples R China; 18.Zhejiang Univ, Stem Cell Inst, Hangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Han, Xiaoping,Zhou, Ziming,Fei, Lijiang,et al. Notch signalling drives synovial fibroblast identity and arthritis pathology[J]. NATURE,2020,582(7811):259-+. |
| APA | Han, Xiaoping.,Zhou, Ziming.,Fei, Lijiang.,Sun, Huiyu.,Wang, Renying.,...&Guo, Guoji.(2020).Notch signalling drives synovial fibroblast identity and arthritis pathology.NATURE,582(7811),259-+. |
| MLA | Han, Xiaoping,et al."Notch signalling drives synovial fibroblast identity and arthritis pathology".NATURE 582.7811(2020):259-+. |
| 条目包含的文件 | 条目无相关文件。 | |||||
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