Single‐cell transcriptomics reveals pathogenic dysregulation of previously unrecognised chondral stem/progenitor cells in children with microtia

作者：Jing Ma, Yu Zhang, Zijun Yan, Peixuan Wu, Chenlong Li, Run Yang, Xinyu Lu, Xin Chen, Aijuan He, Yaoyao Fu, Duan Ma, Weidong Tian, Tianyu Zhang · 发表于：Clinical and Translational Medicine · 年份：2022 · DOI：10.1002/ctm2.702 · 被引用次数：12 · 研究领域：Reconstructive Facial Surgery Techniques、Ear Surgery and Otitis Media、Nasal Surgery and Airway Studies

To the Editor: Microtia, a common craniofacial birth defect worldwide, results from auricular cartilage dysplasia and is accompanied with several unfortunate physical and psychological consequences for children.1 However, existing treatments have adverse outcomes and its pathogenesis is poorly understood.2 Because characterisation of cell type composition and function in auricular cartilage can increase our understanding of microtia,3, 4 we conducted the first single-cell transcriptomic survey in these tissues. We collected auricular cartilage of three children with microtia and six normal controls (NC; two children, four adults), then analysed the transcriptomes of 47 214 total cells after stringent quality control (Figure 1A and Figure S1A–F; Table S1). We detected seven cell types through unsupervised clustering analysis combined with previous reports of cell type-specific marker genes (Figure 1B and Figure S1G). The four cartilage-related cell types included quiescent chondral stem/progenitor cells (CSPCs; expressing EGR15 HES1,6 COL2A1 and CYTL1), which could directly differentiate into chondrocytes (Chonds; COL2A1 and CYTL1); quiescent stromal stem/progenitor cells (SSPCs; EGR1, HES1, COL1A1 and LUM) and stromal cells (SCs; COL1A1 and LUM), whereas other cell types included immune cells, perivascular cells and endothelial cells (Figure 1C,D and Figures S1H,J and S2; Table S2). Gene ontology (GO) terms enriched in the above cell types also showed their specific functions...