Li Xinyu, Li Datao, Zhang Ruhong
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sci Rep. 2025 Jan 6;15(1):1021. doi: 10.1038/s41598-025-85169-x.
Microtia is a congenital malformation characterized by underdevelopment of the external ear. While chondrocyte dysfunction has been implicated in microtia, the specific cellular abnormalities remain poorly understood. This study aimed to investigate mitochondrial dysfunction in microtia chondrocytes using single-cell RNA sequencing. Cartilage samples were obtained from patients with unilateral, non-syndromic microtia and healthy controls. Single-cell RNA sequencing was performed using the 10 × Genomics platform. Bioinformatic analyses including cell type identification, trajectory analysis, and gene co-expression network analysis were conducted. Mitochondrial function was assessed through ROS levels, membrane potential, and transmission electron microscopy. Chondrocytes from microtia samples showed lower mitochondrial function scores compared to normal samples. Trajectory analysis revealed more disorganized differentiation patterns in microtia chondrocytes. Mitochondrial dysfunction in microtia chondrocytes was confirmed by increased ROS production, decreased membrane potential, and altered mitochondrial structure. Gene co-expression network analysis identified hub genes associated with mitochondrial function, including SDHA, SIRT1, and PGC1A, which showed reduced expression in microtia chondrocytes. This study provides evidence of mitochondrial dysfunction in microtia chondrocytes and identifies potential key genes involved in this process. These findings offer new insights into the pathogenesis of microtia and may guide future therapeutic strategies.
小耳畸形是一种以耳廓发育不全为特征的先天性畸形。虽然软骨细胞功能障碍与小耳畸形有关，但具体的细胞异常仍知之甚少。本研究旨在利用单细胞RNA测序研究小耳畸形软骨细胞中的线粒体功能障碍。从单侧非综合征性小耳畸形患者和健康对照者获取软骨样本。使用10×基因组学平台进行单细胞RNA测序。进行了包括细胞类型鉴定、轨迹分析和基因共表达网络分析在内的生物信息学分析。通过活性氧水平、膜电位和透射电子显微镜评估线粒体功能。与正常样本相比，小耳畸形样本中的软骨细胞线粒体功能评分较低。轨迹分析显示小耳畸形软骨细胞的分化模式更加紊乱。活性氧生成增加、膜电位降低和线粒体结构改变证实了小耳畸形软骨细胞中的线粒体功能障碍。基因共表达网络分析确定了与线粒体功能相关的枢纽基因，包括SDHA、SIRT1和PGC1A，这些基因在小耳畸形软骨细胞中的表达降低。本研究提供了小耳畸形软骨细胞中线粒体功能障碍的证据，并确定了参与这一过程的潜在关键基因。这些发现为小耳畸形的发病机制提供了新的见解，并可能指导未来的治疗策略。
