Urinary single-cell sequencing captures kidney injury and repair processes in human acute kidney injury
Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved..
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.
| Errataetall: |
CommentIn: Kidney Int. 2022 Dec;102(6):1219-1221. - PMID 36411018 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:102 |
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| Enthalten in: |
Kidney international - 102(2022), 6 vom: 15. Dez., Seite 1359-1370 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Klocke, Jan [VerfasserIn] |
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| Links: |
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| Themen: |
Acute kidney injury |
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| Anmerkungen: |
Date Completed 23.11.2022 Date Revised 10.01.2023 published: Print-Electronic CommentIn: Kidney Int. 2022 Dec;102(6):1219-1221. - PMID 36411018 Citation Status MEDLINE |
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| doi: |
10.1016/j.kint.2022.07.032 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345669223 |
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| 520 | |a Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Kim, Seung Joon |e verfasserin |4 aut | |
| 700 | 1 | |a Skopnik, Christopher M |e verfasserin |4 aut | |
| 700 | 1 | |a Hinze, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Boltengagen, Anastasiya |e verfasserin |4 aut | |
| 700 | 1 | |a Metzke, Diana |e verfasserin |4 aut | |
| 700 | 1 | |a Grothgar, Emil |e verfasserin |4 aut | |
| 700 | 1 | |a Prskalo, Luka |e verfasserin |4 aut | |
| 700 | 1 | |a Wagner, Leonie |e verfasserin |4 aut | |
| 700 | 1 | |a Freund, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Görlich, Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Muench, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt-Ott, Kai M |e verfasserin |4 aut | |
| 700 | 1 | |a Mashreghi, Mir-Farzin |e verfasserin |4 aut | |
| 700 | 1 | |a Kocks, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Eckardt, Kai-Uwe |e verfasserin |4 aut | |
| 700 | 1 | |a Rajewsky, Nikolaus |e verfasserin |4 aut | |
| 700 | 1 | |a Enghard, Philipp |e verfasserin |4 aut | |
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