The diagnosis of focal segmental glomerulosclerosis (FSGS) requires a renal biopsy, which is invasive and can be problematic in children and in some adults. We used single cell RNA-sequencing to explore disease-related cellular signatures in 23 urine samples from 12 FSGS subjects. We identified immune cells, predominantly monocytes, and renal epithelial cells, including podocytes. Analysis revealed M1 and M2 monocyte subsets, and podocytes showing high expression of genes for epithelial-to-mesenchymal transition (EMT). We confirmed M1 and M2 gene signatures using published monocyte/macrophage data from lupus nephritis and cancer. Using renal transcriptomic data from the Nephrotic Syndrome Study Network (NEPTUNE), we found that urine cell immune and EMT signature genes showed higher expression in FSGS biopsies compared to minimal change disease biopsies. These results suggest that urine cell profiling may serve as a diagnostic and prognostic tool in nephrotic syndrome and aid in identifying novel biomarkers and developing personalized therapeutic strategies.

中文翻译：

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局部节段性肾小球硬化中的尿单细胞RNA测序显示免疫细胞和足细胞的炎症特征

局灶性节段性肾小球硬化症（FSGS）的诊断需要肾脏活检，这是有创性的，可能对儿童和某些成人有问题。我们使用单细胞RNA测序来探索来自12名FSGS受试者的23个尿液样本中与疾病相关的细胞特征。我们鉴定了免疫细胞，主要是单核细胞，以及肾上皮细胞，包括足细胞。分析显示M1和M2单核细胞亚群，足细胞显示上皮-间充质转化（EMT）基因的高表达。我们使用来自狼疮肾炎和癌症的单核细胞/巨噬细胞数据，证实了M1和M2基因签名。利用来自肾病综合症研究网络（NEPTUNE）的肾脏转录组数据，我们发现，与最小变化疾病活检相比，尿液免疫和EMT签名基因在FSGS活检中显示出更高的表达。这些结果表明，尿细胞谱分析可以作为肾病综合征的诊断和预后工具，并有助于鉴定新的生物标志物和制定个性化的治疗策略。