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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.


  
Mott and generalized Wigner crystal states in WSe2/WS2 moire superlattices 期刊论文
NATURE, 2020, 579 (7799) : 359-+
作者:  Yuan, Jie;  Chang, Si-Yuan;  Yin, Shi-Gang;  Liu, Zhi-Yang;  Cheng, Xiu;  Liu, Xi-Juan;  Jiang, Qiang;  Gao, Ge;  Lin, De-Ying;  Kang, Xin-Lei;  Ye, Shi-Wei;  Chen, Zheng;  Yin, Jiang-An;  Hao, Pei;  Jiang, Lubin;  Cai, Shi-Qing
收藏  |  浏览/下载:50/0  |  提交时间:2020/07/03

Strongly correlated insulating Mott and generalized Wigner phases are detected in WSe2/WS2 moire superlattices, and their electrical properties and excited spin states are studied using an optical technique.


Moire superlattices can be used to engineer strongly correlated electronic states in two-dimensional van der Waals heterostructures, as recently demonstrated in the correlated insulating and superconducting states observed in magic-angle twisted-bilayer graphene and ABC trilayer graphene/boron nitride moire superlattices(1-4). Transition metal dichalcogenide moire heterostructures provide another model system for the study of correlated quantum phenomena(5) because of their strong light-matter interactions and large spin-orbit coupling. However, experimental observation of correlated insulating states in this system is challenging with traditional transport techniques. Here we report the optical detection of strongly correlated phases in semiconducting WSe2/WS2 moire superlattices. We use a sensitive optical detection technique and reveal a Mott insulator state at one hole per superlattice site and surprising insulating phases at 1/3 and 2/3 filling of the superlattice, which we assign to generalized Wigner crystallization on the underlying lattice(6-11). Furthermore, the spin-valley optical selection rules(12-14) of transition metal dichalcogenide heterostructures allow us to optically create and investigate low-energy excited spin states in the Mott insulator. We measure a very long spin relaxation lifetime of many microseconds in the Mott insulating state, orders of magnitude longer than that of charge excitations. Our studies highlight the value of using moire superlattices beyond graphene to explore correlated physics.


  
The genome of Chenopodium quinoa (vol 542, pg 307, 2017) 期刊论文
NATURE, 2017, 545 (7655) : 510-510
作者:  Jarvis, David E.;  Ho, Yung Shwen;  Lightfoot, Damien J.;  Schmockel, Sandra M.;  Li, Bo;  Borm, Theo J. A.;  Ohyanagi, Hajime;  Mineta, Katsuhiko;  Michell, Craig T.;  Saber, Noha;  Kharbatia, Najeh M.;  Rupper, Ryan R.;  Sharp, Aaron R.;  Dally, Nadine;  Boughton, Berin A.;  Woo, Yong H.;  Gao, Ge;  Schijlen, Elio G. W. M.;  Guo, Xiujie;  Momin, Afaque A.;  Negrao, Sonia;  Al-Babili, Salim;  Gehring, Christoph;  Roessner, Ute;  Jung, Christian;  Murphy, Kevin;  Arold, Stefan T.;  Gojobori, Takashi;  van der Linden, C. Gerard;  van Loo, Eibertus N.;  Jellen, Eric N.;  Maughan, Peter J.;  Tester, Mark
收藏  |  浏览/下载:10/0  |  提交时间:2019/04/09
The genome of Chenopodium quinoa 期刊论文
NATURE, 2017, 542 (7641) : 307-+
作者:  Jarvis, David E.;  Ho, Yung Shwen;  Lightfoot, Damien J.;  Schmockel, Sandra M.;  Li, Bo;  Borm, Theo J. A.;  Ohyanagi, Hajime;  Mineta, Katsuhiko;  Michell, Craig T.;  Saber, Noha;  Kharbatia, Najeh M.;  Rupper, Ryan R.;  Sharp, Aaron R.;  Dally, Nadine;  Boughton, Berin A.;  Woo, Yong H.;  Gao, Ge;  Schijlen, Elio G. W. M.;  Guo, Xiujie;  Momin, Afaque A.;  Negrao, Sonia;  Al-Babili, Salim;  Gehring, Christoph;  Roessner, Ute;  Jung, Christian;  Murphy, Kevin;  Arold, Stefan T.;  Gojobori, Takashi;  van der Linden, C. Gerard;  van Loo, Eibertus N.;  Jellen, Eric N.;  Maughan, Peter J.;  Tester, Mark
收藏  |  浏览/下载:8/0  |  提交时间:2019/04/09