title: Identification of adult nephron progenitors capable of kidney regeneration in zebrafish.
abstract: Loss of kidney function underlies many renal diseases. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Cuong Q
authors.initials: CQ
authors.lastname: Diep
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ma
authors.forename: Rahul C
authors.initials: RC
authors.lastname: Deo
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Holm
authors.forename: Richard W
authors.initials: RW
authors.lastname: Naylor
authors.forename: Natasha
authors.initials: N
authors.lastname: Arora
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Wingert
authors.forename: Frank
authors.initials: F
authors.lastname: Bollig
authors.forename: Gordana
authors.initials: G
authors.lastname: Djordjevic
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lichman
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikenaga
authors.forename: Fumihito
authors.initials: F
authors.lastname: Ono
authors.forename: Christoph
authors.initials: C
authors.lastname: Englert
authors.forename: Chad A
authors.initials: CA
authors.lastname: Cowan
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hukriede
authors.forename: Robert I
authors.initials: RI
authors.lastname: Handin
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Davidson
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D007668:Kidney / Q000166:cytology* / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism; D007814:Larva; D023421:Models, Animal; D009399:Nephrons / Q000166:cytology* / Q000254:growth & development; D038081:Organogenesis; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D015027:Zebrafish / Q000254:growth & development*