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

J Park, R Shrestha, C Qiu, A Kondo, S Huang, M Werth… - Science, 2018 - science.org
J Park, R Shrestha, C Qiu, A Kondo, S Huang, M Werth, M Li, J Barasch, K Suszták
Science, 2018science.org
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 …
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.
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