Single-cell RNA-seq profiling reveals novel insights in immune-complex deposition and epithelium transition in IgA nephropathy

IgA nephropathy represents the most prevalent chronic nephrosis worldwide. However, pathogenesis about IgA deposition and end-stage renal failure is still not well defined. Using single-cell RNA-seq, we identified the mesangial membrane receptor for IgA, which collaborates with increased extracellular matrix proteins and protease inhibitor to facilitate IgA deposition. Meanwhile, cell-cell interaction analysis revealed increased communications between mesangium and other cell types, uncovering how morbidity inside glomerulus spreads to whole kidney, which results in the genetic changes of kidney resident immune cells. Prominent interaction decreasing in intercalated cells leads to the discovery of a transitional cell type, which exhibited significant EMT and fibrosis features. Our work comprehensively characterized the pathological mesangial signatures, highlighting the step-by-step pathogenic process of IgA nephropathy from mesangium to epithelium. In this study, we collected single cells from 13 IgAN patients’ renal biopsies and normal renal cells from 6 kidney cancer patients’ paracancerous tissues. As glomerulus are difficult to digest, we separately dissociated the glomerulus and the rest renal tissues. We applied CD326+ and CD14+ MACS to capture epithelium and macrophages, to cover the entire renal cell types, negative selected cells from MACS were also collected. Meanwhile, we isolated monocytes from 5 of the 13 IgAN patients and another 5 normal persons’ peripheral blood using CD14+ MACS **Submitter declares that the raw data have been deposited in the Genome Sequence Archive for Human (https://bigd.big.ac.cn/gsa-human/) under submission number PRJCA003506.**