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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.


  
DNA-loop extruding condensin complexes can traverse one another 期刊论文
NATURE, 2020
作者:  Li, Xun;  Zhang, Fei;  He, Haiying;  Berry, Joseph J.;  Zhu, Kai;  Xu, Tao
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

Condensin, a key component of the structure maintenance of chromosome (SMC) protein complexes, has recently been shown to be a motor that extrudes loops of DNA(1). It remains unclear, however, how condensin complexes work together to collectively package DNA into chromosomes. Here we use time-lapse single-molecule visualization to study mutual interactions between two DNA-loop-extruding yeast condensins. We find that these motor proteins, which, individually, extrude DNA in one direction only are able to dynamically change each other'  s DNA loop sizes, even when far apart. When they are in close proximity, condensin complexes are able to traverse each other and form a loop structure, which we term a Z-loop-three double-stranded DNA helices aligned in parallel with one condensin at each edge. Z-loops can fill gaps left by single loops and can form symmetric dimer motors that pull in DNA from both sides. These findings indicate that condensin may achieve chromosomal compaction using a variety of looping structures.


Single-molecule visualization shows that condensin-a motor protein that extrudes DNA in one direction only-can encounter and pass a second condensin molecule to form a new type of DNA loop that gathers DNA from both sides.


  
The gut microbiome in atherosclerotic cardiovascular disease 期刊论文
NATURE COMMUNICATIONS, 2017, 8
作者:  Jie, Zhuye;  Xia, Huihua;  Zhong, Shi-Long;  Feng, Qiang;  Li, Shenghui;  Liang, Suisha;  Zhong, Huanzi;  Liu, Zhipeng;  Gao, Yuan;  Zhao, Hui;  Zhang, Dongya;  Su, Zheng;  Fang, Zhiwei;  Lan, Zhou;  Li, Junhua;  Xiao, Liang;  Li, Jun;  Li, Ruijun;  Li, Xiaoping;  Li, Fei;  Ren, Huahui;  Huang, Yan;  Peng, Yangqing;  Li, Guanglei;  Wen, Bo;  Dong, Bo;  Chen, Ji-Yan;  Geng, Qing-Shan;  Zhang, Zhi-Wei;  Yang, Huanming;  Wang, Jian;  Wang, Jun;  Zhang, Xuan;  Madsen, Lise;  Brix, Susanne;  Ning, Guang;  Xu, Xun;  Liu, Xin;  Hou, Yong;  Jia, Huijue;  He, Kunlun;  Kristiansen, Karsten
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/27
Whole-genome resequencing of 472 Vitis accessions for grapevine diversity and demographic history analyses 期刊论文
NATURE COMMUNICATIONS, 2019, 10
作者:  Liang, Zhenchang;  Duan, Shengchang;  Sheng, Jun;  Zhu, Shusheng;  Ni, Xuemei;  Shao, Jianhui;  Liu, Chonghuai;  Nick, Peter;  Du, Fei;  Fan, Peige;  Mao, Ruzhi;  Zhu, Yifan;  Deng, Weiping;  Yang, Min;  Huang, Huichuan;  Liu, Yixiang;  Ding, Yiqing;  Liu, Xianju;  Jiang, Jianfu;  Zhu, Youyong;  Li, Shaohua;  He, Xiahong;  Chen, Wei;  Dong, Yang
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
Targeted emission reductions from global super-polluting power plant units 期刊论文
NATURE SUSTAINABILITY, 2018, 1 (1) : 59-68
作者:  Tong, Dan;  Zhang, Qiang;  Davis, Steven J.;  Liu, Fei;  Zheng, Bo;  Geng, Guannan;  Xue, Tao;  Li, Meng;  Hong, Chaopeng;  Lu, Zifeng;  Streets, David G.;  Guan, Dabo;  He, Kebin
收藏  |  浏览/下载:11/0  |  提交时间:2020/08/19