Ligament Cell Atlas: Single-cell nuclear transcriptome sequencing analysis of ligamentum teres for human developmental dysplasia of the hip

Cell number: 22,884

Cell types: Receptor−like cells, Endotheliocytes, Ligament stem cells, Pericytes, Macrophage, Fibroblasts

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Developmental Dysplasia of the Hip (DDH) is one of the common musculoskeletal disorders in children. If the diagnosis and treatment of DDH patients are delayed, the patients will have an abnormal gait, acetabular dysplasia, spinal deformity, and avascular necrosis of the femoral head. What is worse, DDH patients who are delayed in treatment may even develop femoral deformity and hip osteoarthritis. DDH may be caused by multiple factors, such as genetic susceptibility and acquired environmental factors, but the exact genetic model and pathogenesis of DDH are still unclear. Thickening and hypertrophy of the round ligament are common pathological changes in DDH. In patients with DDH, the thickened, hypertrophic ligamentum teres occupy the acetabular fossa, thereby impeding the femoral head reduction. In this study, we used snRNA-Seq for the first time to dissect cellular heterogeneity in the round ligament of patients with DDH. We summarized the susceptibility or candidate genes that may have been associated with DDH disease in the past and screened out eight susceptibility or candidate genes for DDH that were differentially expressed in different cell types of the round ligament. Most of these eight genes belong to ECM regulation-related genes and are highly expressed in Ligament stem cells, suggesting that Ligament stem cells may play an essential role in developing DDH. In addition, we dig deep into the interaction information between different cell types in the round ligament through intercellular communication network analysis. We found close intercellular interactions among these six types of cells. In addition, we explored the expression of ligand-receptor pairs of interest in different cell types. Finally, we deposited the single-cell nuclear transcriptome sequencing data of the round ligament of DDH in the MSKCA database (www.mskca.tech/Ligament) and visualized it interactively. The findings of this study will provide new ideas and methods for diagnosing and treating DDH.