Single-cell chromatin accessibility atlas of adult developmental dysplasia of hip

doi:10.3877/cma.j.issn.1674-134X.2025.05.007

Abstract

Abstract:

Objective

To elucidate the epigenetic regulatory mechanisms underlying acetabular cartilage dysplasia and chondrocyte degradation in patients with developmental dysplasia of hip (DDH) using single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) technology and provide new insights into the cell-specific molecular pathology of DDH.

Methods

A total of 64 053 acetabular chondrocytes were collected from six DDH patients (those with a history of hip surgery, infection, or systemic diseases were excluded) and six patients with traumatic femoral neck fracture (TNOF) as controls in Xi’an Honghui Hospital. These cells were analyzed by scATAC-seq to construct a map of genome-wide single-cell chromatin accessibility and reveal cellular heterogeneity. The differences in the proportions of cell types between the two groups were analyzed using Mann-Whitney U test.

Results

Six distinct cell populations in DDH cartilage were identified, such as fibrocartilage chondrocytes (FC), homeostatic chondrocytes (HomC), prehypertrophic chondrocytes (preHTC) and hypertrophic chondrocyte (HTC) as well as regulatory chondrocytes (RegC). The percentage of FC (U=35, P=0.004), HomC (U=36, P=0.002) and preHTC (U=35, P=0.004) were significantly higher in the DDH group than those in the control group. While compared to the control group, the percentage of RegC was remarkably lower in the DDH group (U=1, P=0.004). Disease associated candidate differentially accessible peaks and transcription factors (TF) were revealed, such as HINFP (log₂ FC= 2.84, P=6.31×10⁻⁴) for HomC population and runt related transcription factor 2 (RUNX2) (log₂ FC=1.02, P=1.95×10⁻⁵) for RegC population.

Conclusions

The identified cell types exerted different influences on the development of DDH, which may be driven by corresponding key transcription factor of differential accessible peaks. These findings may provide novel clues for understanding etiology and pathogenesis as well as therapeutic targets of DDH.

Key words: Single-cell analysis, Hip dislocation, congenital, Chondrocytes

Ke Xu, Xuena Yang, Shiqiang Cheng, Weikun Hou, Lin Liu, Kan Peng, Yan Wen, Yumeng Jia, Feng Zhang, Peng Xu. Single-cell chromatin accessibility atlas of adult developmental dysplasia of hip[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2025, 19(05): 570-579.

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URL: https://zhgjwkzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-134X.2025.05.007

https://zhgjwkzz.cma-cmc.com.cn/EN/Y2025/V19/I05/570

Figures/Tables 5

Figure 1 X-ray images of typical DDH patients. A is a pelvic radiograph at anteroposterior view; B is a radiograph of hip joint at lateral view

Figure 2 UMAP diagram of ScATAC-seq data setNote: color coding represents distinct cell populations identified through scRNA-seq clustering analysis. EC-effector chondrocytes; FC-ibrocartilage chondrocytes; HomC-homeostatic chondrocytes; HTC-hypertrophic chondrocytes; preHTC-prehypertrophic chondrocytes; RegC-regulatory chondrocytes

Figure 3 UMAP visualization and cell proportion of each cell type in DDH group and control group. A is UMAP visualization of ScATAC-seq, divided into DDH group and control group; B is percentage of each cell type in DDH group and control group; C is the proportion of each cell type in DDH group and control groupNote: EC-effector chondrocytes; FC-fibrocartilage chondrocytes; HomC-homeostatic chondrocytes; HTC-hypertrophic chondrocytes; preHTC-prehypertrophic chondrocytes; RegC-regulatory chondrocytes; ns-P>0.05；^**-P<0.01

Figure 4 Volcano plots showing genes associated with differentially accessible peaks between DDH and control groups across cell types. A is EC; B is FC; C is HomC; D is HTC; E is preHTC; F is RegCNote: EC-effector chondrocytes; FC-fibrocartilage chondrocytes; HomC-homeostatic chondrocytes; HTC-hypertrophic chondrocytes; preHTC-prehypertrophic chondrocytes; RegC-regulatory chondrocytes

Figure 5 KEGG pathway enrichment analysis of genes associated with differentially accessible peaks between DDH and control groups across cell types, showing significantly enriched KEGG pathways. A is EC; B is FC; C is HTC; D is RegCNote: EC-effector chondrocytes; FC-ibrocartilage chondrocytes; HTC-hypertrophic chondrocytes; RegC-regulatory chondrocytes

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