Lineage tracing reveals transient phenotypic adaptation of tubular cells during acute kidney injury

Marc Buse, Mingbo Cheng, Vera Jankowski, Michaela Lellig, Viktor Sterzer, Thiago Strieder, Katja Leuchtle, Ina V. Martin, Claudia Seikrit, Paul Brinkkoettter, Giuliano Crispatzu, Jürgen Floege, Peter Boor, Timotheus Speer, Rafael Kramann, Tammo Ostendorf, Marcus J. Moeller, Ivan G. Costa, Eleni Stamellou*

*Corresponding author for this work

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Abstract

Tubular injury is the hallmark of acute kidney injury (AKI) with a tremendous impact on patients and health-care systems. During injury, any differentiated proximal tubular cell (PT) may transition into a specific injured phenotype, so-called “scattered tubular cell” (STC)-phenotype. To understand the fate of this specific phenotype, we generated transgenic mice allowing inducible, reversible, and irreversible tagging of these cells in a murine AKI model, the unilateral ischemia-reperfusion injury (IRI). For lineage tracing, we analyzed the kidneys using single-cell profiling during disease development at various time points. Labeled cells, which we defined by established endogenous markers, already appeared 8 h after injury and showed a distinct expression set of genes. We show that STCs re-differentiate back into fully differentiated PTs upon the resolution of the injury. In summary, we show the dynamics of the phenotypic transition of PTs during injury, revealing a reversible transcriptional program as an adaptive response during disease.

Original languageEnglish
Article number109255
JournaliScience
Volume27
Issue number3
DOIs
Publication statusPublished - 15 Mar 2024

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