Temporal transcriptome features identify early skeletal commitment during human epiphysis development at single-cell resolution
Zhonghao Deng,
Shengwei Rong,
Lu Gan,
Fuhua Wang,
Liangxiao Bao,
Fang Cai,
Zheting Liao,
Yu Jin,
Shuhao Feng,
Zihang Feng,
Yiran Wei,
Ruge Chen,
Yangchen Jin,
Yanli Zhou,
Xiaoyong Zheng,
Liping Huang,
Liang Zhao
Affiliations
Zhonghao Deng
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Shengwei Rong
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Lu Gan
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Fuhua Wang
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Liangxiao Bao
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Fang Cai
Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital Taihe Branch, Guangzhou, Guangdong 510515, China
Zheting Liao
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Yu Jin
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Shuhao Feng
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Zihang Feng
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Yiran Wei
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Ruge Chen
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Yangchen Jin
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China
Yanli Zhou
Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong 510515, China
Xiaoyong Zheng
Orthopaedic Department, The 8th medical center of Chinese PLA General Hospital, Beijing 100091, China
Liping Huang
Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong 510515, China; Corresponding author
Liang Zhao
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Orthopaedic Surgery, Shunde First People Hospital, Foshan, Guangdong 528300, China; Corresponding author
Summary: Human epiphyseal development has been mainly investigated through radiological and histological approaches, uncovering few details of cellular temporal genetic alternations. Using single-cell RNA sequencing, we investigated the dynamic transcriptome changes during post-conception weeks (PCWs) 15–25 of human distal femoral epiphysis cells. We find epiphyseal cells contain multiple subtypes distinguished by specific markers, gene signatures, Gene Ontology (GO) enrichment analysis, and gene set variation analysis (GSVA). We identify the populations committed to cartilage or ossification at this time, although the secondary ossification centers (SOCs) have not formed. We describe the temporal alternation in transcriptional expression utilizing trajectories, transcriptional regulatory networks, and intercellular communication analyses. Moreover, we find the emergence of the ossification-committed population is correlated with the COL2A1-(ITGA2/11+ITGB1) signaling. NOTCH signaling may contribute to the formation of cartilage canals and ossification via NOTCH signaling. Our findings will advance the understanding of single-cell genetic changes underlying fetal epiphysis development.
