Single-cell transcriptomic analysis reveals impaired mitochondrial gene expression in the podocytes of a child with primary coenzyme Q10 nephropathy.

Abstract

Background Coenzyme Q10 (CoQ10) nephropathy is a well-known cause of hereditary steroid-resistant nephrotic syndrome, primarily impacting podocytes. This study aimed to elucidate variations in individual cell-level gene expression in CoQ10 nephropathy using single-cell transcriptomics. Methods We conducted single-cell sequencing of a kidney biopsy specimen from a 5-year-old boy diagnosed with a CoQ10 nephropathy caused by a compound heterozygous COQ2 mutation. The analysis focused on the proportion of cell types, differentially expressed genes in each cell type, changes in gene expression related to mitochondrial function and oxidative phosphorylation (OXPHOS). Results Our findings revealed a uniform downregulation of mitochondrial gene expression across various cell types in the context of these mutations. Notably, there was a specific decrease in mitochondrial gene expression across all cell types. The study also highlighted an altered immune cell population proportion attributed to the COQ2 gene mutation. Pathway analysis indicated a downregulation in OXPHOS and an upregulation of various synthesis pathways, particularly in podocytes. Conclusion This study improves our understanding of CoQ10 nephropathy's pathogenesis and highlights the potential applications of single-cell sequencing in hereditary kidney diseases.