LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma.
LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma.
复制标题
DOI：
10.1016/j.cell.2022.03.011
复制
发表时间：
2022-04-14
期刊：
影响因子：
64.5
通讯作者：
Amit I
中科院分区：
文献类型：
--
作者：
Gur C;Wang SY;Sheban F;Zada M;Li B;Kharouf F;Peleg H;Aamar S;Yalin A;Kirschenbaum D;Braun-Moscovici Y;Jaitin DA;Meir-Salame T;Hagai E;Kragesteen BK;Avni B;Grisariu S;Bornstein C;Shlomi-Loubaton S;David E;Shreberk-Hassidim R;Molho-Pessach V;Amar D;Tzur T;Kuint R;Gross M;Barboy O;Moshe A;Fellus-Alyagor L;Hirsch D;Addadi Y;Erenfeld S;Biton M;Tzemach T;Elazary A;Naparstek Y;Tzemach R;Weiner A;Giladi A;Balbir-Gurman A;Amit I
Systemic sclerosis (scleroderma, SSc) is an incurable autoimmune disease with high morbidity and mortality rates. Here, we conducted a population-scale single-cell genomic analysis of skin and blood samples of 56 healthy controls and 97 SSc patients at different stages of the disease. We found immune compartment dysfunction only in a specific subtype of diffuse SSc patients but global dysregulation of the stromal compartment, particularly in a previously undefined subset of LGR5+-scleroderma-associated fibroblasts (ScAFs). ScAFs are perturbed morphologically and molecularly in SSc patients. Single-cell multiome profiling of stromal cells revealed ScAF-specific markers, pathways, regulatory elements, and transcription factors underlining disease development. Systematic analysis of these molecular features with clinical metadata associates specific ScAF targets with disease pathogenesis and SSc clinical traits. Our high-resolution atlas of the sclerodermatous skin spectrum will enable a paradigm shift in the understanding of SSc disease and facilitate the development of biomarkers and therapeutic strategies.
登录
查看更多内容
DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
影响因子：
27.4
作者：
Gaydosik AM;Tabib T;Domsic R;Khanna D;Lafyatis R;Fuschiotti P
通讯作者：
Fuschiotti P
影响因子：
15.3
作者：
GABBIANI, G;RYAN, GB;STATKOV, PR;HIRSCHEL, BJ;MAJNO, G
通讯作者：
MAJNO, G
影响因子：
4.6
作者：
Jang, Bo Gun;Kim, Hye Sung;Kang, Gyeong Hoon
通讯作者：
Kang, Gyeong Hoon
影响因子：
82.9
作者：
Cohen YC;Zada M;Wang SY;Bornstein C;David E;Moshe A;Li B;Shlomi-Loubaton S;Gatt ME;Gur C;Lavi N;Ganzel C;Luttwak E;Chubar E;Rouvio O;Vaxman I;Pasvolsky O;Ballan M;Tadmor T;Nemets A;Jarchowcky-Dolberg O;Shvetz O;Laiba M;Shpilberg O;Dally N;Avivi I;Weiner A;Amit I
通讯作者：
Amit I