Abstract
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.