TY  - BOOK
AU  - Gur,Chamutal
AU  - Wang,Shuang-Yin
AU  - Sheban,Fadi
AU  - Zada,Mor
AU  - Li,Baoguo
AU  - Kharouf,Fadi
AU  - Peleg,Hagit
AU  - Aamar,Suhail
AU  - Yalin,Adam
AU  - Kirschenbaum,Daniel
AU  - Braun-Moscovici,Yolanda
AU  - Jaitin,Diego Adhemar
AU  - meir-salame,Tomer
AU  - Hagai,Efrat
AU  - Kragesteen,Bjørt K.
AU  - Avni,Batia
AU  - Grisariu,Sigal
AU  - Bornstein,Chamutal
AU  - Shlomi-Loubaton,Shir
AU  - David,Eyal
AU  - Shreberk-Hassidim,Rony
AU  - Molho-Pessach,Vered
AU  - Amar,Dalit
AU  - Tzur,Tomer
AU  - Kuint,Rottem
AU  - Gross,Moshe
AU  - Barboy,Oren
AU  - Moshe,Adi
AU  - Fellus-Alyagor,Liat
AU  - Hirsch,Dana
AU  - Addadi,Yoseph
AU  - Erenfeld,Shlomit
AU  - Biton,Moshe
AU  - Tzemach,Tehila
AU  - Elazary,Anat
AU  - Naparstek,Yaakov
AU  - Tzemach,Reut
AU  - Weiner,Assaf
AU  - Giladi,Amir
AU  - Balbir-Gurman,Alexandra
AU  - Amit,Ido
TI  - LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma
PY  - 2022///-04-14
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7612792; /pubmed/35381199
N2  - 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
UR  - http://dx.doi.org/10.1016/j.cell.2022.03.011
ER  -