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| Status |
Public on Nov 10, 2024 |
| Title |
Single Cell RNA Sequencing of Synovial Tissue in Adolescents Undergoing ACL Reconstruction |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Synovial tissue biopsies were obtained during ACL reconstruction from six patients, enzymatically digested to obtain heterogenous single-cell suspensions, and analyzed by scRNA-seq. The six scRNA-seq samples as well as eleven other patient samples were categorized into three Immunotypes based on flow cytometry quantification of the immune cells present in the synovium tissue. The scRNA-seq output was analyzed for a more comprehensive characterization of the cell types present as well as the relative expression of select inflammatory markers and immunomodulatory genes.
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| Contributor(s) |
Sarah R, Guangxu J, Nury S, Bailey F, Jonathan R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Oct 29, 2024 |
| Last update date |
Nov 11, 2024 |
| Contact name |
Sarah Romereim |
| Organization name |
Atrium Health
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| Department |
Musculoskeletal Institute
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| Street address |
1000 Blythe Blvd, CRC 305
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| City |
Charlotte |
| State/province |
NC |
| ZIP/Postal code |
28203 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| GSM8599997 |
Synovium, Immunotype 1, Sample 78, scRNA-seq |
| GSM8599998 |
Synovium, Immunotype 2, Sample 80, scRNA-seq |
| GSM8599999 |
Synovium, Immunotype 3, Sample 84, scRNA-seq |
| GSM8600000 |
Synovium, Immunotype 1, Sample 85, scRNA-seq |
| GSM8600001 |
Synovium, Immunotype 2, Sample 93, scRNA-seq |
| GSM8600002 |
Synovium, Immunotype 3, Sample 95, scRNA-seq |
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| Relations |
| BioProject |
PRJNA1179366 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE280537_RAW.tar |
2.8 Gb |
(http)(custom) |
TAR (of H5, JSON) |
| GSE280537_aggregation.csv.gz |
149 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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