Journal
ISCIENCE
Volume 26, Issue 8, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2023.107200
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Using single-cell RNA sequencing, the study explores the transcriptome changes of human distal femoral epiphysis cells during post-conception weeks 15-25. Multiple subtypes of epiphyseal cells are identified, and their characteristics and functions are analyzed. The study also investigates the role of specific signaling pathways in the development of cartilage and ossification. The findings provide valuable insights into the genetic changes that occur during fetal epiphysis development.
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.
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