Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
J Cell Mol Med. 2021 May;25(10):4684-4695. doi: 10.1111/jcmm.16407. Epub 2021 Mar 22.
Glomerulonephritis is the one of the major causes of the end-stage kidney disease, whereas the pathological process of glomerulonephritis is still not completely understood. Single-cell RNA sequencing (scRNA-seq) emerges to be a powerful tool to evaluate the full heterogeneity of kidney diseases. To reveal cellular gene expression profiles of glomerulonephritis, we performed scRNA-seq of 2 human kidney transplantation donor samples, 4 human glomerulonephritis samples, 1 human malignant hypertension (MH) sample and 1 human chronic interstitial nephritis (CIN) sample, all tissues were taken from the biopsy. After filtering the cells with < 200 genes and > 10% mitochondria (MT) genes, the resulting 14 932 cells can be divided into 20 cell clusters, consistently with the previous report, in disease samples dramatic immune cells infiltration was found, among which a proximal tubule (PT) subset characterized by wnt-β catenin activation and a natural killer T (NKT) subset high expressing LTB were found. Furthermore, in the cluster of the podocyte, three glomerulonephritis related genes named FXYD5, CD74 and B2M were found. Compared with the mesangial of donor, the gene CLIC1 and RPS26 were up-regulated in mesangial of IgA nephropathy(IgAN), whereas the gene JUNB was up-regulated in podocyte of IgAN in comparison with that of donor. Meanwhile, some membranous nephropathy (MN) high expressed genes such as HLA-DRB5, HLA-DQA2, IFNG, CCL2 and NR4A2, which involve in highest enrichment pathway, display the cellular-specific expression style, whereas monocyte marker of lupus nephritis (LN) named TNFSF13B was also found and interferon alpha/beta signalling pathway was enriched in B and NKT of LN comparing with donor. By scRNA-seq, we first defined the podocyte markers of glomerulonephritis and specific markers in IgA, MN and LN were found at cellular level. Furthermore, the critical role of interferon alpha/beta signalling pathway was enriched in B and NKT of LN was declared.
肾小球肾炎是终末期肾病的主要病因之一，而肾小球肾炎的病理过程仍不完全清楚。单细胞 RNA 测序 (scRNA-seq) 已成为评估肾脏疾病全异质性的有力工具。为了揭示肾小球肾炎的细胞基因表达谱，我们对 2 例人类肾移植供体样本、4 例人类肾小球肾炎样本、1 例人类恶性高血压 (MH) 样本和 1 例人类慢性间质性肾炎 (CIN) 样本进行了 scRNA-seq 分析，所有组织均取自活检。在过滤掉细胞<200 个基因和>10%线粒体 (MT) 基因后，得到的 14932 个细胞可以分为 20 个细胞簇，与之前的报告一致，在疾病样本中发现了明显的免疫细胞浸润，其中一个近端肾小管 (PT) 亚群表现为 wnt-β 连环蛋白激活，自然杀伤 T (NKT) 亚群高表达 LTB。此外，在足细胞簇中，发现了三个与肾小球肾炎相关的基因，分别命名为 FXYD5、CD74 和 B2M。与供体相比，IgA 肾病 (IgAN) 系膜中基因 CLIC1 和 RPS26 上调，而 IgAN 足细胞中基因 JUNB 上调。同时，一些膜性肾病 (MN) 高表达基因，如 HLA-DRB5、HLA-DQA2、IFNG、CCL2 和 NR4A2，涉及最高富集途径，显示出细胞特异性表达模式，而狼疮肾炎 (LN) 的单核细胞标记物 TNFSF13B 也被发现，并且 IFN-α/β 信号通路在 LN 的 B 和 NKT 中富集与供体相比。通过 scRNA-seq，我们首次定义了肾小球肾炎的足细胞标记物，并在细胞水平上发现了 IgA、MN 和 LN 的特定标记物。此外，还证实了 IFN-α/β 信号通路在 LN 的 B 和 NKT 中发挥了关键作用。
