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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:43/0  |  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.


  
Recycling and metabolic flexibility dictate life in the lower oceanic crust 期刊论文
NATURE, 2020, 579 (7798) : 250-+
作者:  Zhou, Peng;  Yang, Xing-Lou;  Wang, Xian-Guang;  Hu, Ben;  Zhang, Lei;  Zhang, Wei;  Si, Hao-Rui;  Zhu, Yan;  Li, Bei;  Huang, Chao-Lin;  Chen, Hui-Dong;  Chen, Jing;  Luo, Yun;  Guo, Hua;  Jiang, Ren-Di;  Liu, Mei-Qin;  Chen, Ying;  Shen, Xu-Rui;  Wang, Xi;  Zheng, Xiao-Shuang;  Zhao, Kai;  Chen, Quan-Jiao;  Deng, Fei;  Liu, Lin-Lin;  Yan, Bing;  Zhan, Fa-Xian;  Wang, Yan-Yi;  Xiao, Geng-Fu;  Shi, Zheng-Li
收藏  |  浏览/下载:37/0  |  提交时间:2020/05/13

The lithified lower oceanic crust is one of Earth'  s last biological frontiers as it is difficult to access. It is challenging for microbiota that live in marine subsurface sediments or igneous basement to obtain sufficient carbon resources and energy to support growth(1-3) or to meet basal power requirements(4) during periods of resource scarcity. Here we show how limited and unpredictable sources of carbon and energy dictate survival strategies used by low-biomass microbial communities that live 10-750 m below the seafloor at Atlantis Bank, Indian Ocean, where Earth'  s lower crust is exposed at the seafloor. Assays of enzyme activities, lipid biomarkers, marker genes and microscopy indicate heterogeneously distributed and viable biomass with ultralow cell densities (fewer than 2,000 cells per cm(3)). Expression of genes involved in unexpected heterotrophic processes includes those with a role in the degradation of polyaromatic hydrocarbons, use of polyhydroxyalkanoates as carbon-storage molecules and recycling of amino acids to produce compounds that can participate in redox reactions and energy production. Our study provides insights into how microorganisms in the plutonic crust are able to survive within fractures or porous substrates by coupling sources of energy to organic and inorganic carbon resources that are probably delivered through the circulation of subseafloor fluids or seawater.


  
Estimating ground-level CO concentrations across China based on the national monitoring network and MOPITT: potentially overlooked CO hotspots in the Tibetan Plateau 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2019, 19 (19) : 12413-12430
作者:  Liu, Dongren;  Di, Baofeng;  Luo, Yuzhou;  Deng, Xunfei;  Zhang, Hanyue;  Yang, Fumo;  Grieneisen, Michael L.;  Zhan, Yu
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27
LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling 期刊论文
SCIENCE, 2019, 364 (6440) : 545-+
作者:  Choi, Jin Huk;  Zhong, Xue;  McAlpine, William;  Liao, Tzu-Chieh;  Zhang, Duanwu;  Fang, Beibei;  Russell, Jamie;  Ludwig, Sara;  Nair-Gill, Evan;  Zhang, Zhao;  Wang, Kuan-wen;  Misawa, Takuma;  Zhan, Xiaoming;  Choi, Mihwa;  Wang, Tao;  Li, Xiaohong;  Tang, Miao;  Sun, Qihua;  Yu, Liyang;  Murray, Anne R.;  Moresco, Eva Marie Y.;  Beutler, Bruce
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator 期刊论文
SCIENCE, 2018, 362 (6421) : 1375-+
作者:  Guo, Ang;  Wang, Yihui;  Chen, Biyi;  Wang, Yunhao;  Yuan, Jinxiang;  Zhang, Liyang;  Hall, Duane;  Wu, Jennifer;  Shi, Yun;  Thu, Qi;  Chen, Cheng;  Thiel, William H.;  Than, Xin;  Weiss, Robert M.;  Zhan, Fenghuang;  Musselman, Catherine A.;  Pufall, Miles;  Zhu, Weizhong;  Au, Kin Fai;  Hong, Jiang;  Anderson, Mark E.;  Grueter, Chad E.;  Song, Long-Sheng
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Emission-driven changes in anthropogenic aerosol concentrations in China during 1970-2010 and its implications for PM2.5 control policy 期刊论文
ATMOSPHERIC RESEARCH, 2018, 212: 106-119
作者:  Chang, Wenyuan;  Zhan, Jianqiong;  Zhang, Ying;  Li, Zhengqiang;  Xing, Jia;  Li, Jiandong
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/09
PM2.5  Historical aerosols  Multi-model simulations  Air quality  
Structure of a human catalytic step I spliceosome 期刊论文
SCIENCE, 2018, 359 (6375) : 537-544
作者:  Zhan, Xiechao;  Yan, Chuangye;  Zhang, Xiaofeng;  Lei, Jianlin;  Shi, Yigong
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Azimuthal Distribution of Deep Convection, Environmental Factors, and Tropical Cyclone Rapid Intensification: A Perspective from HWRF Ensemble Forecasts of Hurricane Edouard (2014) 期刊论文
JOURNAL OF THE ATMOSPHERIC SCIENCES, 2018, 75 (1) : 275-295
作者:  Leighton, Hua;  Gopalakrishnan, Sundararaman;  Zhang, Jun A.;  Rogers, Robert F.;  Zhang, Zhan;  Tallapragada, Vijay
收藏  |  浏览/下载:4/0  |  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