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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.


  
Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells 期刊论文
NATURE, 2020, 577 (7792) : 676-+
作者:  Zhao, Ruozhu;  Chen, Xin;  Ma, Weiwei;  Zhang, Jinyu;  Guo, Jie;  Zhong, Xiu;  Yao, Jiacheng;  Sun, Jiahui;  Rubinfien, Julian;  Zhou, Xuyu;  Wang, Jianbin;  Qi, Hai
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)(1,2), but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics(3,4), cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.


Stress induces hair greying in mice through depletion of melanocyte stem cells, which is mediated by the activation of sympathetic nerves rather than through immune attack or adrenal stress hormones.


  
Ground-to-satellite quantum teleportation 期刊论文
NATURE, 2017, 549 (7670) : 70-+
作者:  Ren, Ji-Gang;  Xu, Ping;  Yong, Hai-Lin;  Zhang, Liang;  Liao, Sheng-Kai;  Yin, Juan;  Liu, Wei-Yue;  Cai, Wen-Qi;  Yang, Meng;  Li, Li;  Yang, Kui-Xing;  Han, Xuan;  Yao, Yong-Qiang;  Li, Ji;  Wu, Hai-Yan;  Wan, Song;  Liu, Lei;  Liu, Ding-Quan;  Kuang, Yao-Wu;  He, Zhi-Ping;  Shang, Peng;  Guo, Cheng;  Zheng, Ru-Hua;  Tian, Kai;  Zhu, Zhen-Cai;  Liu, Nai-Le;  Lu, Chao-Yang;  Shu, Rong;  Chen, Yu-Ao;  Peng, Cheng-Zhi;  Wang, Jian-Yu;  Pan, Jian-Wei
收藏  |  浏览/下载:13/0  |  提交时间:2019/11/27