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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.


  
New Generation of Climate Models Track Recent Unprecedented Changes in Earth's Radiation Budget Observed by CERES 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (5)
作者:  Loeb, Norman G.;  Wang, Hailan;  Allan, Richard P.;  Andrews, Timothy;  Armour, Kyle;  Cole, Jason N. S.;  Dufresne, Jean-Louis;  Forster, Piers;  Gettelman, Andrew;  Guo, Huan;  Mauritsen, Thorsten;  Ming, Yi;  Paynter, David;  Proistosescu, Cristian;  Stuecker, Malte F.;  Willen, Ulrika;  Wyser, Klaus
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/02
Decomposing Shortwave Top-of-Atmosphere and Surface Radiative Flux Variations in Terms of Surface and Atmospheric Contributions 期刊论文
JOURNAL OF CLIMATE, 2019, 32 (16) : 5003-5019
作者:  Loeb, Norman G.;  Wang, Hailan;  Rose, Fred G.;  Kato, Seiji;  Smith, William L., Jr.;  Sun-Mack, Sunny
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Satellite observations  Model evaluation  performance  Climate variability  Interannual variability  
Phase Locking of the Boreal Summer Atmospheric Response to Dry Land Surface Anomalies in the Northern Hemisphere 期刊论文
JOURNAL OF CLIMATE, 2019, 32 (4) : 1081-1099
作者:  Wang, Hailan;  Schubert, Siegfried D.;  Koster, Randal D.;  Chang, Yehui
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/09
Atmosphere-land interaction  Rossby waves  Stationary waves  Topographic effects  Drought  Summer/warm season  
Determining the Shortwave Radiative Flux From Earth Polychromatic Imaging Camera 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2018, 123 (20) : 11479-11491
作者:  Su, Wenying;  Liang, Lusheng;  Doelling, David R.;  Minnis, Patrick;  Duda, David P.;  Khlopenkov, Konstantin;  Thieman, Mandana M.;  Loeb, Norman G.;  Kato, Seiji;  Valero, Francisco P. J.;  Wang, Hailan;  Rose, Fred G.
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
Clouds and the Earth's Radiant Energy System (CERES) Energy Balanced and Filled (EBAF) Top-of-Atmosphere (TOA) Edition-4.0 Data Product 期刊论文
JOURNAL OF CLIMATE, 2018, 31 (2) : 895-918
作者:  Loeb, Norman G.;  Doelling, David R.;  Wang, Hailan;  Su, Wenying;  Nguyen, Cathy;  Corbett, Joseph G.;  Liang, Lusheng;  Mitrescu, Cristian;  Rose, Fred G.;  Kato, Seiji
收藏  |  浏览/下载:10/0  |  提交时间:2019/04/09
History of winning remodels thalamo-PFC circuit to reinforce social dominance 期刊论文
SCIENCE, 2017, 357 (6347) : 162-+
作者:  Zhou, Tingting;  Zhu, Hong;  Fan, Zhengxiao;  Wang, Fei;  Chen, Yang;  Liang, Hexing;  Yang, Zhongfei;  Zhang, Lu;  Lin, Longnian;  Zhan, Yang;  Wang, Zheng;  Hu, Hailan
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27