Objectives Transcriptomic data demonstrated that fibroblasts are heterogeneous with functionally diverse subpopulations. Although fibroblasts are key effector cells of fibrotic diseases such as systemic sclerosis (SSc), they have not yet been characterised spatially at the cellular level. Here, we aimed to investigate fibroblast subpopulations using imaging mass cytometry (IMC) as a proteomic-based, spatially resolved omics approach. Methods We applied IMC to deconvolute the heterogeneity of 49 969 cells including 6501 fibroblasts at the single-cell level, to analyse their spatial distribution and to characterise their cellular niches in skin sections of patients with SSc and controls in situ. Results We identified 13 different subpopulations of fibroblasts in SSc and control skin, the proportion increases in five fibroblast subpopulations (myofibroblasts, FAP high , S1PR + , Thy1 + ;ADAM12 high ;PU.1 high and ADAM12 + ;GLI1 + fibroblasts) and decreases in three subpopulations (TFAM high , PI16 + ;FAP + and Thy1 + ;ADAM12 low fibroblasts). Several fibroblast subpopulations demonstrated spatial enrichment and altered cellular interactions in SSc. The proportion of S1PR + -fibroblast positively correlated with more extensive skin fibrosis, whereas high numbers of PI16 + ;FAP – -fibroblasts were associated with milder skin fibrosis. The frequency of aberrant cellular interaction between S1PR + and ADAM12 + ;GLI1 + -fibroblasts also positively associated with the extent of skin fibrosis in SSc. Conclusion Using IMC, we demonstrated profound changes in composition and localisation of the majority of fibroblast subpopulations in SSc skin. These findings may provide a rationale for specific targeting of deregulated fibroblast subpopulations in SSc. Quantification of S1PR + -fibroblast and PI16 + ;FAP – -fibroblasts may offer potential for patient stratification according to severity of skin fibrosis.

Aleix Rius Rigau

Minrui Liang

Veda Devakumar

Ranjana Neelagar

Alexandru-Emil Matei

Andrea-Hermina Györfi

Christina Bergmann

Tim Filla

Vladyslav Fedorchenko

Georg Schett

Jörg H W Distler

Yi-Nan Li

Annals of the Rheumatic Diseases

风湿病年鉴 (ARD) 是一份国际同行评审期刊，致力于促进最高标准的科学交流和教育。它涵盖了风湿病学的所有方面，包括肌肉骨骼疾病、关节炎疾病和结缔组织疾病的谱系。 ARD 发表基础、临床和转化科学研究。鼓励简明的科学交流，并以同行评审的国际会议论文集为特色。教育论文包括最先进的评论、“如何”文章和教育案例，重点关注临床实践中面临的问题。该杂志于 1939 年首次出版，拥有权威的全球编辑委员会和不断增长的国际读者群。

The Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal dedicated to promoting the highest standards of scientific communication and education. It covers all aspects of rheumatology, including musculoskeletal disorders, arthritic diseases, and connective tissue diseases. ARD publishes basic, clinical, and translational scientific research, encouraging concise scientific communication and featuring peer-reviewed conference proceedings. Educational papers include cutting-edge reviews, 'how-to' articles, and educational cases, focusing on issues faced in clinical practice. Since its first publication in 1939, the journal has maintained a prestigious global editorial board and a growing international readership.

《Annals of the Rheumatic Diseases》（风湿病年鉴，ARD）是一份国际同行评审的学术期刊，旨在促进高标准的科学交流与教育。期刊涵盖风湿病学的各个方面，包括肌肉骨骼疾病、关节炎和结缔组织疾病等。ARD发表基础研究、临床研究和转化科学研究，鼓励简洁明了的科学交流，并定期刊登国际会议的同行评审论文。教育类论文包括前沿评论、实用指南和教育案例，重点关注临床实践中遇到的问题。该杂志自1939年创刊以来，拥有权威的全球编辑委员会和不断扩大的国际读者群。

Category	Quartile
医学	1
医学, 风湿病学	1

Imaging mass cytometry-based characterisation of fibroblast subsets and their cellular niches in systemic sclerosis

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info