Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease

Bryan Ronald Conway, Eoin O Sullivan, Carolynn Cairns, James O'Sullivan, Daniel Simpson, Angela Salzano, Katie Connor, Peng Ding, Duncan Humphries, Kevin Stewart, Oliver Teenan, Riinu Pius, Neil C Henderson, Cecile Benezech, Prakash Ramachandran, David A Ferenbach, Jeremy Hughes, Tamir Chandra, Laura Denby

Research output: Contribution to journalArticlepeer-review

Abstract

Background Little is known about the roles of myeloid cell subsets in kidney injury and in the limited ability of the organ to repair itself. Characterizing these cells based only on surface markers using flow cytometry might not provide a full phenotypic picture. Defining these cells at the single-cell, transcriptomic level could reveal myeloid heterogeneity in the progression and regression of kidney disease.

Methods Integrated droplet– and plate-based single-cell RNA sequencing were used in the murine, reversible, unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single-cell level during renal injury and the resolution of fibrosis. Paired blood exchange tracked the fate of monocytes recruited to the injured kidney.

Results A single-cell atlas of the kidney generated using transcriptomics revealed marked changes in the proportion and gene expression of renal cell types during injury and repair. Conventional flow cytometry markers would not have identified the 12 myeloid cell subsets. Monocytes recruited to the kidney early after injury rapidly adopt a proinflammatory, profibrotic phenotype that expresses Arg1, before transitioning to become Ccr2+ macrophages that accumulate in late injury. Conversely, a novel Mmp12+ macrophage subset acts during repair.

Conclusions Complementary technologies identified novel myeloid subtypes, based on transcriptomics in single cells, that represent therapeutic targets to inhibit progression or promote regression of kidney disease.
Original languageEnglish
Pages (from-to)2833–2854
JournalJournal of the American Society of Nephrology
Volume31
Issue number12
Early online date8 Oct 2020
DOIs
Publication statusPublished - 1 Dec 2020

Keywords

  • fibrosis
  • kidney disease
  • scRNA sequencing
  • myeloid cells

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