Decoding myofibroblast origins in human kidney fibrosis

C Kuppe, MM Ibrahim, J Kranz, XT Zhang, S Ziegler, J Perales-Paton, J Jansen, KC Reimer, JR Smith, R Dobie, JR Wilson-Kanamori, M Halder, YX (Ying Xin) Xu, N Kabgani, N Kaesler, M Klaus, L Gernhold, VG Puelles, TB Huber, PPC BoorS Menzel, Remco Hoogenboezem, Eric Bindels, J Steffens, J Floege, Rebekka Schneider, J Saez-Rodriguez, NC Henderson, Rafael Kramann

Research output: Contribution to journalArticleAcademicpeer-review

131 Citations (Scopus)

Abstract

Kidney fibrosis is the hallmark of chronic kidney disease progression; however, at present no antifibrotic therapies exist1–3. The origin, functional heterogeneity and regulation of scar-forming cells that occur during human kidney fibrosis remain poorly understood1,2,4. Here, using single-cell RNA sequencing, we profiled the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys to map the entire human kidney. This analysis enabled us to map all matrix-producing cells at high resolution, and to identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single-cell RNA sequencing and ATAC–seq (assay for transposase-accessible chromatin using sequencing) experiments in mice, and spatial transcriptomics in human kidney fibrosis, to shed light on the cellular origins and differentiation of human kidney myofibroblasts and their precursors at high resolution. Finally, we used this strategy to detect potential therapeutic targets, and identified NKD2 as a myofibroblast-specific target in human kidney fibrosis.

Original languageEnglish
Pages (from-to)281-286
Number of pages6
JournalNature
Volume589
Issue number7841
DOIs
Publication statusPublished - 14 Jan 2021

Fingerprint

Dive into the research topics of 'Decoding myofibroblast origins in human kidney fibrosis'. Together they form a unique fingerprint.

Cite this