Single cell profiling in COVID-19 associated acute kidney injury reveals patterns of tubule injury and repair in human

The cellular mechanisms of kidney tubule repair are poorly characterized in human. Here, we applied single-cell RNA sequencing to analyze the kidney in the first days after acute injury in 5 patients with severe COVID19. We found that tubule repair follows two converging patterns involving the plasticity of mature tubule cells and the expansion and differentiation of progenitor-like cells. Tubule repair by cell plasticity displayed substantial similarities between mouse and man and determined the transient expansion of undifferentiated tubule cells with altered functional and metabolic properties. Progenitor-like cells marked by PROM1 proliferated in response to injury and followed a differentiation process characterized by the sequential activation of the WNT, NOTCH and HIPPO signaling pathways. Taken together, our analyses reveal cell state transitions and fundamental cellular hierarchies underlying kidney injury and repair in patients. We characterized by single nucleus RNA sequencing (snRNAseq) kidney biopsies obtained from 5 critically ill patients with COVID-19 before planned withdrawal of resuscitation measures. snRNAseq was carried out by using 10X Genomics Chromium Drop-Seq technology. Illumina Next-Seq sequencing of barcoded single nuclei libraries was performed and aligned to a pre-mrna genome(GRCh38-2020) with STAR/CellRanger. Seurat v4 in R v4 was used for downstream analyses, including normalization, scaling, and clustering of nuclei. The snRNAseq data were integrated with 3 controls from available datasets generated with similar tissue processing and single cell technology for data control and validation .