Troy/TNFRSF19 marks epithelial progenitor cells during mouse kidney development that continue to contribute to turnover in adult kidney

Abstract

During kidney development, progressively committed progenitor cells give rise to the distinct segments of the nephron, the functional unit of the kidney. Similar segment-committed progenitor cells are thought to be involved in the homeostasis of adult kidney. However, markers for most segment-committed progenitor cells remain to be identified. Here, we evaluate Troy/TNFRSF19 as a segment-committed nephron progenitor cell marker. Troy is expressed in the ureteric bud during embryonic development. During postnatal nephrogenesis, Troy⁺ cells are present in the cortex and papilla and display an immature tubular phenotype. Tracing of Troy⁺ cells during nephrogenesis demonstrates that Troy⁺ cells clonally give rise to tubular structures that persist for up to 2 y after induction. Troy⁺ cells have a 40-fold higher capacity than Troy⁻ cells to form organoids, which is considered a stem cell property in vitro. In the adult kidney, Troy⁺ cells are present in the papilla and these cells continue to contribute to collecting duct formation during homeostasis. The number of Troy-derived cells increases after folic acid-induced injury. Our data show that Troy marks a renal stem/progenitor cell population in the developing kidney that in adult kidney contributes to homeostasis, predominantly of the collecting duct, and regeneration.