Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease

By Jihwan Park, Rojesh Shrestha, Chengxiang Qiu, Ayano Kondo, Shizheng Huang, Max Werth, Mingyao Li, J. Barasch, K. Suszták. Science, 2018

955 citations recorded by the source corpus.

Touring the kidney, cell by cell Our kidneys play a critical role in keeping us healthy, a fact of which we are reminded several times each day. This organ's cellular complexity has hindered progress in understanding the mechanisms underlying chronic kidney disease, which affects 10% of the world's population. Using single-cell transcriptional profiling, Park et al. produced a comprehensive cell atlas of the healthy mouse kidney (see the Perspective by Humphreys). An unexpected cell type in the collecting duct appears to be a transitional state between two known cell types. The transition from one cell type to the other is regulated by the Notch signaling pathway and is associated with metabolic acidosis. The authors also find that genetically distinct kidney diseases with common clinical features share common cellular origins. Science, this issue p. 758; see also p. 709 A single-cell atlas of the mouse kidney reveals an unexpected cell type that likely contributes to kidney disease. Our understanding of kidney disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ’s multiple homeostatic functions. To help fill this knowledge gap, we characterized 57,979 cells from healthy mouse kidneys by using unbiased single-cell RNA sequencing. On the basis of gene expression patterns, we infer that inherited kidney diseases that arise from distinct genetic mutations but share the same phenotypic manifestation originate from the same differentiated cell type. We also found that the collecting duct in kidneys of adult mice generates a spectrum of cell types through a newly identified transitional cell. Computational cell trajectory analysis and in vivo lineage tracing revealed that intercalated cells and principal cells undergo transitions mediated by the Notch signaling pathway. In mouse and human kidney disease, these transitions were shifted toward a principal cell fate and were associated with metabolic acidosis.

Subfields: Molecular Biology, Nephrology

View Paper: https://www.semanticscholar.org/paper/eb269862f936040c0822ab6fd2dc78e971ccaa23

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Citations in the corpus

DoubletFinder: Doublet Detection in Single-Cell RNA Sequencing Data Using Artificial Nearest Neighbors (2018, methodology): “Initially, n was set according to the Poisson doublet formation rate, as specified for the particular cell-loading density used in the study (Park et al., 2018).”
Bulk tissue cell type deconvolution with multi-subject single-cell expression reference (2018, background): “X1 (2) X2 (2) X3 (2) X4 (2) ) ( p1 p2 p3 p4 ) + (ε (1) ε((2)) ) , (11)”
A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility. (2018, positive): “(K) Cicero gene activity scores for GWAS disease genes with restricted expression patterns (Park et al., 2018).”