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bioRxiv · 10.1101/2020.03.22.002261

Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury

Kirita, Y.·Wu, H.·Uchimura, K.·Wilson, P.·Humphreys, B.
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Abstract

After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this "failed-repair proximal tubule cell" or FR-PTC, state can be detected in other models of kidney injury, increasing in the aging rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair. Significance StatementSingle nucleus RNA sequencing revealed gene expression changes during repair after acute kidney injury. We describe a small population of proximal tubule cells that fail to repair (FR-PTC). Since this subpopulation expresses abundant pro-inflammatory and profibrotic genes, it may represent a new therapeutic target to improve repair and reduce fibrosis after AKI.

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Kirita, Y., Wu, H., Uchimura, K., Wilson, P., Humphreys, B.. 2020-03-23. Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury. https://doi.org/10.1101/2020.03.22.002261

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