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

Buse, Marc; Cheng, Mingbo; Jankowski, Vera

doi:10.1016/j.isci.2024.109255

Highlights

•The PEC-rtTA marks specifically a regenerative cell type (STC) emerging after AKI

•Lineage tracing revealed that STCs differentiate back into mature tubular cells

•Prolonged activation of the STC phenotype leads to a proinflammatory behavior

•STCs display a heterogeneous cell population

Summary

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.

BioAcyl Corp

WIKINDX Resources

Highlights

Summary