A Partial Picture of the Single-Cell Transcriptomics of Human IgA Nephropathy.

Rong Tang,Peng Jin,Wei Lin,Ping Xiao,Weisheng Peng,Peter J Eggenhuizen,Ting Meng,Zhou Xiao,Qiaoling Zhou,Yangshuo Tang,Yong Zhong,Joshua D Ooi,Jinbiao Chen,Xiang Ding,Chanjuan Shen,Xiang Ao,Xiangcheng Xiao

doi:10.3389/fimmu.2021.645988

Abstract

The molecular mechanisms underlying renal damage of IgA nephropathy (IgAN) remain incompletely defined. Here, single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from IgAN and control subjects to define the transcriptomic landscape at single-cell resolution. We presented a comprehensive scRNA-seq analysis of human renal biopsies from IgAN. We showed for the first time that IgAN mesangial cells displayed increased expression of several novel genes including MALAT1, GADD45B, SOX4, and EDIL3, which were related to cell proliferation and matrix accumulation. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. Furthermore, we compared the results of 4 IgAN patients with the published scRNA-Seq data of healthy kidney tissues of three human donors in order to further validate the findings in our study. The results also verified that the overexpressed genes in tubule cells from IgAN patients were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. The receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. IgAN patients with overt proteinuria displayed elevated genes participating in several signaling pathways compared with microproteinuria group. It needs to be mentioned that based on number of mesangial cells and other kidney cells analyzed in this study, the results of our study are preliminary and needs to be confirmed on larger number of cells from larger number of patients and controls in future studies. Therefore, these results offer new insight into pathogenesis and identify new therapeutic targets for IgAN.

Highlights

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide [1, 2]
We identified leukocytes which were composed of macrophages, monocytes, and dendritic cells in kidney sample of IgAN patients, which was consistent with previous research [29]
We verified that scRNA-seq analysis of kidney sample obtained from IgAN patients was a feasible and effective technique

Summary

Introduction

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide [1, 2]. The fast development of single-cell RNA sequencing (scRNA-seq) technology allows the inquiry of transcriptomic profiles and signaling pathways in diverse cell types from a given sample simultaneously, and unlike bulk RNA-seq, it can define comprehensive gene sets at the single-cell level [9, 10]. This new methodology has been employed in various renal diseases [11,12,13,14]. We applied scRNAseq to kidney samples from patients with IgAN to identify gene expression at the single cell level, and explore novel cellular interactions and crucial molecular pathways contributing to the disease development

Methods

Results

Conclusion