Kidney Single-Cell Atlas Reveals Myeloid Heterogeneity in Progression and Regression of Kidney Disease

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, trans...

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Published in:Journal of the American Society of Nephrology Vol. 31; no. 12; p. 2833
Main Authors: Conway, Bryan R, O'Sullivan, Eoin D, Cairns, Carolynn, O'Sullivan, James, Simpson, Daniel J, Salzano, Angela, Connor, Katie, Ding, Peng, Humphries, Duncan, Stewart, Kevin, Teenan, Oliver, Pius, Riinu, Henderson, Neil C, Bénézech, Cécile, Ramachandran, Prakash, Ferenbach, David, Hughes, Jeremy, Chandra, Tamir, Denby, Laura
Format: Journal Article
Language:English
Published: United States 01.12.2020
Subjects:
Animals
Disease Models, Animal
Disease Progression
Kidney Diseases - etiology
Kidney Diseases - metabolism
Kidney Diseases - pathology
Macrophages - physiology
Male
Mice
Mice, Inbred C57BL
Myeloid Cells - physiology
Sequence Analysis, RNA
Single-Cell Analysis
Ureteral Obstruction - etiology
kidney disease
fibrosis
myeloid cells
scRNA sequencing
ISSN:1533-3450, 1533-3450
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Summary: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. 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. 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 , before transitioning to become macrophages that accumulate in late injury. Conversely, a novel macrophage subset acts during repair. 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.
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ISSN:1533-3450
1533-3450
DOI:10.1681/ASN.2020060806