Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.
OBJECTIVES: To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. METHODS: OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. RESULTS: We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an "arthritis" specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. CONCLUSION: This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.
Duke Scholars
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- Transcriptome
- Synovial Membrane
- Sequence Analysis, RNA
- Osteoarthritis, Knee
- Humans
- Computer Simulation
- Arthritis & Rheumatology
- 4207 Sports science and exercise
- 3202 Clinical sciences
- 1106 Human Movement and Sports Sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcriptome
- Synovial Membrane
- Sequence Analysis, RNA
- Osteoarthritis, Knee
- Humans
- Computer Simulation
- Arthritis & Rheumatology
- 4207 Sports science and exercise
- 3202 Clinical sciences
- 1106 Human Movement and Sports Sciences