Details

Autor(en) / Beteiligte

• Gur, Chamutal
• Wang, Shuang-Yin
• Sheban, Fadi
• Zada, Mor
• Li, Baoguo
• Kharouf, Fadi
• Peleg, Hagit
• Aamar, Suhail
• Yalin, Adam
• Kirschenbaum, Daniel
• Braun-Moscovici, Yolanda
• Jaitin, Diego Adhemar
• meir-salame, Tomer
• Hagai, Efrat
• Kragesteen, Bjørt K.
• Avni, Batia
• Grisariu, Sigal
• Bornstein, Chamutal
• Shlomi-Loubaton, Shir
• David, Eyal
• Shreberk-Hassidim, Rony
• Molho-Pessach, Vered
• Amar, Dalit
• Tzur, Tomer
• Kuint, Rottem
• Gross, Moshe
• Barboy, Oren
• Moshe, Adi
• Fellus-Alyagor, Liat
• Hirsch, Dana
• Addadi, Yoseph
• Erenfeld, Shlomit
• Biton, Moshe
• Tzemach, Tehila
• Elazary, Anat
• Naparstek, Yaakov
• Tzemach, Reut
• Weiner, Assaf
• Giladi, Amir
• Balbir-Gurman, Alexandra
• Amit, Ido

Titel

LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma

Ist Teil von

• Cell, 2022-04, Vol.185 (8), p.1373-1388.e20

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Population-scale scRNA-seq of skin and blood of scleroderma (SSc) disease spectrum•Immune cell composition changes are confined to a specific subtype of dSSc patients•SSc is defined by global perturbation of a novel scleroderma-associated fibroblast (ScAF)•ScAF coordinates the signaling pathways implicated in key processes driving SSc Analysis of skin and blood samples from patients with scleroderma, a severe autoimmune disease, reveals how molecular changes in the stroma rather than immune dysfunction predominantly explain disease severity and clinical features.