Single-cell transcriptomics in a child with coenzyme Q10 nephropathy: potential of single-cell RNA sequencing in pediatric kidney disease.

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 complicated with immune complex-mediated glomerulonephritis. The analysis focused on the proportion of cell types, differentially expressed genes in each cell type, and 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.

Conclusions: This study improves our understanding of CoQ10 nephropathy's pathogenesis and highlights the potential applications of single-cell sequencing in pediatric hereditary kidney diseases.