LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma.
Cell
; 185(8): 1373-1388.e20, 2022 04 14.
Article
em En
| MEDLINE
| ID: mdl-35381199
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
Limite:
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Israel