Park Peong Gang, Choi Sowon, Ahn Yo Han, Kim Seong Heon, Kim Chaeyoon, Kim Hyun Je, Kang Hee Gyung
Department of Pediatrics, Ajou University School of Medicine, Suwon, Republic of Korea.
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Pediatr Nephrol. 2025 May;40(5):1653-1662. doi: 10.1007/s00467-024-06611-2. Epub 2025 Jan 14.
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.
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).
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.
This study improves our understanding of CoQ10 nephropathy's pathogenesis and highlights the potential applications of single-cell sequencing in pediatric hereditary kidney diseases.
辅酶Q10（CoQ10）肾病是遗传性类固醇抵抗性肾病综合征的一个众所周知的病因，主要影响足细胞。本研究旨在使用单细胞转录组学阐明CoQ10肾病中个体细胞水平基因表达的变化。
我们对一名5岁男孩的肾活检标本进行了单细胞测序，该男孩被诊断为因复合杂合COQ2突变导致的CoQ10肾病，并伴有免疫复合物介导的肾小球肾炎。分析重点在于细胞类型比例、每种细胞类型中的差异表达基因，以及与线粒体功能和氧化磷酸化（OXPHOS）相关的基因表达变化。
我们的研究结果显示，在这些突变的背景下，各种细胞类型中线粒体基因表达均呈一致下调。值得注意的是，所有细胞类型中线粒体基因表达均有特定程度的降低。该研究还表明，COQ2基因突变导致免疫细胞群体比例发生变化。通路分析表明氧化磷酸化下调，各种合成通路上调，尤其是在足细胞中。
本研究增进了我们对CoQ10肾病发病机制的理解，并突出了单细胞测序在儿童遗传性肾脏疾病中的潜在应用。
