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

iScience (Aug 2023)

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

Journal volume & issue: Vol. 26, no. 8
p. 107200

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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