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Urinary single-cell sequencing captures kidney injury and repair processes in human acute kidney injury

Item Type:Article
Title:Urinary single-cell sequencing captures kidney injury and repair processes in human acute kidney injury
Creators Name:Klocke, J. and Kim, S.J. and Skopnik, C.M. and Hinze, C. and Boltengagen, A. and Metzke, D. and Grothgar, E. and Prskalo, L. and Wagner, L. and Freund, P. and Görlich, N. and Muench, F. and Schmidt-Ott, K.M. and Mashreghi, M.F. and Kocks, C. and Eckardt, K.U. and Rajewsky, N. and Enghard, P.
Abstract:Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells. Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers. Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting. We analyzed 42,608 single cell transcriptomes of 40 urine samples from 32 patients with AKI and compared our data with reference material from human AKI post-mortem biopsies and published mouse data. We demonstrate that tubular epithelial cells transcriptomes mirror kidney pathology and reflect distinct injury and repair processes, including oxidative stress, inflammation, and tissue rearrangement. We also describe an AKI-specific abundant urinary excretion of adaptive progenitor-like cells. Thus, single cell transcriptomics of kidney cells excreted in urine provides noninvasive, unprecedented insight into cellular processes underlying AKI, thereby opening novel opportunities for target identification, AKI sub-categorization, and monitoring of natural disease course and interventions.
Keywords:Acute Kidney Injury, Distal Tubule, Gene Expression, Animals, Mice
Source:Kidney International
ISSN:0085-2538
Publisher:Nature Publishing Group
Date:29 August 2022
Official Publication:https://doi.org/10.1016/j.kint.2022.07.032
PubMed:View item in PubMed

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