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Single cell RNA-seq of human synovium from patients with anterior cruciate ligament rupture

ABSTRACT: Single-cell RNA sequencing (scRNA-seq) was performed on human synovial tissues obtained from patients with anterior cruciate ligament rupture (ACLR) to characterize cellular programs associated with synovial tissue states. Osteoarthritis (OA) is a heterogeneous joint disease exhibiting substantial variability in synovial inflammation, vascularization, and fibrotic remodeling. In this study, synovial tissue samples from ACLR patients undergoing surgery were enzymatically dissociated and subjected to single-cell RNA sequencing. Publicly available scRNA-seq datasets of OA synovium were used for comparison. These single-cell transcriptomic data were generated as part of a broader effort to investigate cellular heterogeneity in synovial tissue and its relationship to tissue microenvironments and disease pathology. The dataset provides a resource for comparative analysis of synovial cellular composition and may facilitate the identification of cell populations and signaling pathways associated with synovial remodeling and inflammation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE327891 | GEO | 2026/08/31

REPOSITORIES: GEO

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Project description:Background: Loss of motion and arthrofibrosis after anterior cruciate ligament reconstruction (ACLR) can be a devastating complication for athletes. The cellular and molecular pathogenesis of arthrofibrosis is poorly understood, limiting prevention and treatment options. Synovial inflammation may contribute to post-ACLR arthrofibrosis. Hypothesis/Purpose: We hypothesized that higher synovial immune cell infiltration and inflammatory/catabolic gene expression patterns at the time of ACLR would correlate with poorer motion-related outcomes. Study Design: Case Series Methods: Patients aged 10-18 undergoing primary ACLR were enrolled in a prospective pilot study, and synovial tissue biopsies were obtained during ACLR. Flow cytometry and single cell RNA-sequencing explored synovial cell types/frequencies and gene expression. Principle component analysis followed by clustering grouped patients into distinct immunophenotypes based on their synovial cell composition. Clinical follow-up with knee range of motion (ROM), need for lysis of adhesions, and patient reported outcome measures were collected and compared between immunophenotypes. Results: Enrolled patients (n = 17) underwent ACLR at a median of 37 days post-injury. Analysis revealed three distinct immunophenotypes. Type 1 comprised patients with the longest time between injury and surgery and the lowest hematopoietic and T cell infiltration. Types 2 and 3 had similar times between injury and surgery, and Type 2 had intermediate while Type 3 had the highest hematopoietic and T cell percentages. Type 3 was associated with worse ROM at 2- and 6-weeks post-op; T cell prevalence and ROM were inversely correlated at those time points. The only patient requiring lysis of adhesions for arthrofibrosis was in Type 3. Conclusion: Synovial immune infiltration after ACL injury shows variability between patients that clusters into three immunophenotypes correlating with early ROM and the risk of arthrofibrosis. T cell recruitment and infiltration was the strongest factor correlated with ROM outcomes and presents an exciting venue for future research on post-ACLR arthrofibrosis.

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Single cell RNA-seq of human synovium from patients with anterior cruciate ligament rupture

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