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

TY - JOUR

T1 - Troy/TNFRSF19 marks epithelial progenitor cells during mouse kidney development that continue to contribute to turnover in adult kidney

AU - Schutgens, Frans

AU - Rookmaaker, Maarten B

AU - Blokzijl, Francis

AU - van Boxtel, Ruben

AU - Vries, Robert R G

AU - Cuppen, Edwin

AU - Verhaar, Marianne C

AU - Clevers, Hans

PY - 2017/12/26

Y1 - 2017/12/26

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1073/pnas.1714145115

DO - 10.1073/pnas.1714145115

M3 - Article

C2 - 29237753

SN - 0027-8424

VL - 114

SP - E11190-E11198

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 52

ER -