Single-cell regulatory dynamics of the osteoarthritis knee joint

• Applicant: Professorin Dr. Eleftheria Zeggini
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery ; Epidemiology and Medical Biometry/Statistics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497062616

Osteoarthritis is a degenerative joint disease with a huge public health burden and no curative therapy. This project aims to catalyse a step-change in our understanding of cell type-specific regulatory changes underpinning knee osteoarthritis. We will characterise for the first time both transcriptomes and epigenomes of single-cell populations across different stages of cartilage degeneration, as defined by the OARSI grading system. Nuclei will be isolated from primary cartilage derived from 20 osteoarthritis patients undergoing knee replacement surgery. We will jointly perform scRNA-seq and scATAC-seq on the same cell in a total of 600,000 cells across three different OARSI grades. We will characterise cell types across the disease progression spectrum at unprecedented scale and investigate for the first time the chondrocyte epigenetic profile. We will map the activity of regulatory elements by jointly generating a single-cell chromatin accessibility and expression atlas and explore gene regulatory interactions. We will assess changes across the disease severity spectrum to identify disease drivers. This work will generate novel insights into the regulatory mechanisms underpinning this debilitating disease.

• DFG Programme: Research Grants