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Single-cell transcriptomics analysis reveals distinct pathophysiology of the primary coenzyme Q10 nephropathy in pediatric SRNS patient

ABSTRACT: Background: Coenzyme Q10 (COQ10) nephropathy is a well-known cause of hereditary steroid-resistant nephrotic syndrome (SRNS), 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 kidney biopsy specimen on a 5-year-old boy diagnosed with a COQ10 nephropathy caused by 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), and pathway analysis. 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 increase in glycolysis-related gene expression in podocytes. 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 enhances our understanding of the pathogenesis of COQ10 nephropathy and underscore potential therapeutic targets for primary COQ10 nephropathy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270701 | GEO | 2025/04/02

REPOSITORIES: GEO

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Project description:Our present study reveals significant decelerating effects on senescence processes in middle-aged SAMP1 mice supplemented for 6 or 14 months with the reduced form (QH2, 500 mg/ kg BW/ day) of coenzyme Q10 (CoQ10). To unravel molecular mechanisms of these CoQ10 effects, a genome-wide transcript profiling in liver, heart, brain and kidney of SAMP1 mice supplemented with the reduced (QH2) or oxidized form of CoQ10 (Q10) was performed. Liver seems to be the main target tissue of CoQ10 intervention, followed by kidney, heart and brain. Stringent evaluation of the resulting data revealed that QH2 has a stronger impact on gene expression than Q10, which was primarily due to differences in the bioavailability. Indeed, we found that QH2 supplementation was more effective than Q10 to increase levels of CoQ10 in the liver of SAMP1 mice (54.92-fold and 30.36-fold, respectively). To identify functional and regulatory connections of the âtop 50â (p < 0.05) up- and down-regulated QH2-sensitive transcripts in liver (fold changes ranging from 21.24 to -6.12), text mining analysis (Genomatix BiblioSphere, GFG level B3) was used. Hereby, we identified 11 QH2-sensitive genes which are regulated by PPAR-Î± and are primarily involved in cholesterol synthesis (e.g. HMGCS1, HMGCL, HMGCR), fat assimilation (FABP5), lipoprotein metabolism (PLTP) and inflammation (STAT-1). Thus, we provide evidence that QH2 is involved in the reduction of fat and cholesterol synthesis via modulation of the PPAR-Î± signalling pathway. These data may explain, at least in part, the observed effects on decelerated age-dependent degeneration processes in QH2-supplemented SAMP1 mice. Whole genome expression profiles were analysed from liver, heart, brain and kidney (each analyzed separately) of SAMP1 mice supplemented with QH2, Q10 or a control diet. From every experimental group, three mice each were sacrificed 6 or 14 months after supplementation, resulting in a total of 72 microarrays.

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Single-cell transcriptomics analysis reveals distinct pathophysiology of the primary coenzyme Q10 nephropathy in pediatric SRNS patient

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