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Notch signalling drives synovial fibroblast identity and arthritis pathology 期刊论文
NATURE, 2020, 582 (7811) : 259-+
作者:  Han, Xiaoping;  Zhou, Ziming;  Fei, Lijiang;  Sun, Huiyu;  Wang, Renying;  Chen, Yao;  Chen, Haide;  Wang, Jingjing;  Tang, Huanna;  Ge, Wenhao;  Zhou, Yincong;  Ye, Fang;  Jiang, Mengmeng;  Wu, Junqing;  Xiao, Yanyu;  Jia, Xiaoning;  Zhang, Tingyue;  Ma, Xiaojie;  Zhang, Qi;  Bai, Xueli;  Lai, Shujing;  Yu, Chengxuan;  Zhu, Lijun;  Lin, Rui;  Gao, Yuchi;  Wang, Min;  Wu, Yiqing;  Zhang, Jianming;  Zhan, Renya;  Zhu, Saiyong;  Hu, Hailan;  Wang, Changchun;  Chen, Ming;  Huang, He;  Liang, Tingbo;  Chen, Jianghua;  Wang, Weilin;  Zhang, Dan;  Guo, Guoji
收藏  |  浏览/下载:42/0  |  提交时间:2020/07/03

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.


  
Torsional refrigeration by twisted, coiled, and supercoiled fibers 期刊论文
SCIENCE, 2019, 366 (6462) : 216-+
作者:  Wang, Run;  Fang, Shaoli;  Xiao, Yicheng;  Gao, Enlai;  Jiang, Nan;  Li, Yaowang;  Mou, Linlin;  Shen, Yanan;  Zhao, Wubin;  Li, Sitong;  Fonseca, Alexandre F.;  Galvao, Douglas S.;  Chen, Mengmeng;  He, Wenqian;  Yu, Kaiqing;  Lu, Hongbing;  Wang, Xuemin;  Qian, Dong;  Aliev, Ali E.;  Li, Na;  Haines, Carter S.;  Liu, Zhongsheng;  Mu, Jiuke;  Wang, Zhong;  Yin, Shougen;  Lima, Marcio D.;  An, Baigang;  Zhou, Xiang;  Liu, Zunfeng;  Baughman, Ray H.
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
Afro-Eurasian Intermediate-Frequency Teleconnection and Modulation by ENSO 期刊论文
JOURNAL OF CLIMATE, 2018, 31 (19) : 8121-8139
作者:  He, Shan;  Yang, Song;  Lu, Mengmeng;  Li, Zhenning
收藏  |  浏览/下载:3/0  |  提交时间:2019/04/09
Possible effect of the Tibetan Plateau on the "upstream" climate over West Asia, North Africa, South Europe and the North Atlantic 期刊论文
CLIMATE DYNAMICS, 2018, 51 (4) : 1485-1498
作者:  Lu, Mengmeng;  Yang, Song;  Li, Zhenning;  He, Bian;  He, Shan;  Wang, Ziqian
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Tibetan plateau  Heating and response  Atmospheric teleconnection  Climate variations  
Characteristics of surface ozone and nitrogen oxides at urban, suburban and rural sites in Ningbo, China 期刊论文
ATMOSPHERIC RESEARCH, 2017, 187
作者:  Tong, Lei;  Zhang, Huiling;  Yu, Jie;  He, Mengmeng;  Xu, Nengbin;  Zhang, Jingjing;  Qian, Feizhong;  Feng, Jiayong;  Xiao, Hang
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Ozone  Nitrogen oxides  Ningbo  Spatiotemporal variations  Meteorological parameters