Integrative single-cell analysis reveals transcriptional and epigenetic regulatory features of human developmental dysplasia of the hip

Objective: Developmental dysplasia of the hip (DDH) is a developmental disorder that has long-term chronic pain and limited hip joint mobility. The aim of the current study is to understand the specific chondrocyte composition involved in DDH development, identify effective biomarkers for DDH prediction, and elucidate the gene regulatory elements driving DDH progression. Method: In this study, we performed an integrated analysis combining single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing to investigate the molecular programs and epigenetic changes governing human DDH pathogenesis. Validation of marker genes for distinct chondrocyte populations was performed via immunohistochemical assays, alongside characterization of regulatory elements specific to DDH. Results: Our analysis identified seven molecularly distinct chondrocyte populations in DDH cartilage, including a novel inflammatory chondrocyte population with unique molecular signatures. Furthermore, we reconstructed the differentiation trajectory of chondrocytes, shedding light on their roles in DDH pathogenesis. Integrative analyses of transcriptomic and chromatin accessibility profiles highlighted shared regulatory features and transcriptional programs among chondrocyte subtypes, with several regulatory elements linked to DDH progression. Immunohistochemical validation corroborated the presence of key marker genes in distinct chondrocyte subsets. Conclusion: Our findings contribute to clarifying the cellular heterogeneity of DDH and offer insights into potential early diagnostic and therapeutic strategies for this condition.