Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 52, Pages E11190-E11198Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1714145115
Keywords
kidney; stem cell; development; organoids; lineage tracing
Categories
Funding
- Dutch Kidney Foundation [DKF14OP04]
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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.
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