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"... researchers ... have shown that supporting cells called fibroblasts, long viewed as uniform background players, are in fact extremely varied and vital. A subset of these cells, according to the study, may lie at the origins of scleroderma – a rare autoimmune disease. The findings open a new direction for developing a future therapy against this devastating, incurable disorder. ...
Aside from roles in growth and wound healing, fibroblasts were thought to be mere “scaffolding” holding cells in place. The new study challenges this humdrum picture: The researchers found that fibroblasts can be divided into about ten major groups, each performing different and often vital functions, from conveying immune system signals to affecting metabolism, blood clotting and blood vessel formation. These groups can be further broken into some 200 subtypes.
Most importantly, the researchers managed to identify a subset of fibroblast whose concentration drops sharply in the early stages of scleroderma. They named these cells Scleroderma-Associated Fibroblasts, abbreviated as ScAFs (which is also short for “scaffold”). Whereas in healthy controls ScAFs accounted for nearly 30 percent of all fibroblasts, this percentage decreased dramatically in scleroderma patients and continued to plummet as the disease progressed. ..."
Aside from roles in growth and wound healing, fibroblasts were thought to be mere “scaffolding” holding cells in place. The new study challenges this humdrum picture: The researchers found that fibroblasts can be divided into about ten major groups, each performing different and often vital functions, from conveying immune system signals to affecting metabolism, blood clotting and blood vessel formation. These groups can be further broken into some 200 subtypes.
Most importantly, the researchers managed to identify a subset of fibroblast whose concentration drops sharply in the early stages of scleroderma. They named these cells Scleroderma-Associated Fibroblasts, abbreviated as ScAFs (which is also short for “scaffold”). Whereas in healthy controls ScAFs accounted for nearly 30 percent of all fibroblasts, this percentage decreased dramatically in scleroderma patients and continued to plummet as the disease progressed. ..."
From the 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."
"In healthy skin (left), ScAFs feature long, thin extensions (green). In patients with limited scleroderma (center), and even more so, in those with diffuse scleroderma (right), the numbers of ScAFs are reduced. They gradually lose their elongated extensions and develop altered expression levels of certain proteins (blue, red)"
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