Identification of adult nephron progenitors capable of kidney regeneration in zebrafish

Cuong Q. Diep, Dongdong Ma, Rahul C. Deo, Teresa M. Holm, Richard W. Naylor, Natasha Arora, Rebecca A. Wingert, Frank Bollig, Gordana Djordjevic, Benjamin Lichman, Hao Zhu, Takanori Ikenaga, Fumihito Ono, Christoph Englert, Chad A. Cowan, Neil A. Hukriede, Robert I. Handin, Alan J. Davidson

Research output: Contribution to journalArticle

164 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalNature
Volume470
Issue number7332
DOIs
StatePublished - Feb 3 2011

Fingerprint

Nephrons
Zebrafish
Regeneration
Kidney
Stem Cells
Transplantation
Mammals
Cell Engineering
Green Fluorescent Proteins
Larva
Fishes

ASJC Scopus subject areas

  • General

Cite this

Diep, C. Q., Ma, D., Deo, R. C., Holm, T. M., Naylor, R. W., Arora, N., ... Davidson, A. J. (2011). Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature, 470(7332), 95-101. https://doi.org/10.1038/nature09669

Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. / Diep, Cuong Q.; Ma, Dongdong; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Arora, Natasha; Wingert, Rebecca A.; Bollig, Frank; Djordjevic, Gordana; Lichman, Benjamin; Zhu, Hao; Ikenaga, Takanori; Ono, Fumihito; Englert, Christoph; Cowan, Chad A.; Hukriede, Neil A.; Handin, Robert I.; Davidson, Alan J.

In: Nature, Vol. 470, No. 7332, 03.02.2011, p. 95-101.

Research output: Contribution to journalArticle

Diep, CQ, Ma, D, Deo, RC, Holm, TM, Naylor, RW, Arora, N, Wingert, RA, Bollig, F, Djordjevic, G, Lichman, B, Zhu, H, Ikenaga, T, Ono, F, Englert, C, Cowan, CA, Hukriede, NA, Handin, RI & Davidson, AJ 2011, 'Identification of adult nephron progenitors capable of kidney regeneration in zebrafish', Nature, vol. 470, no. 7332, pp. 95-101. https://doi.org/10.1038/nature09669
Diep CQ, Ma D, Deo RC, Holm TM, Naylor RW, Arora N et al. Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature. 2011 Feb 3;470(7332):95-101. https://doi.org/10.1038/nature09669
Diep, Cuong Q. ; Ma, Dongdong ; Deo, Rahul C. ; Holm, Teresa M. ; Naylor, Richard W. ; Arora, Natasha ; Wingert, Rebecca A. ; Bollig, Frank ; Djordjevic, Gordana ; Lichman, Benjamin ; Zhu, Hao ; Ikenaga, Takanori ; Ono, Fumihito ; Englert, Christoph ; Cowan, Chad A. ; Hukriede, Neil A. ; Handin, Robert I. ; Davidson, Alan J. / Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. In: Nature. 2011 ; Vol. 470, No. 7332. pp. 95-101.
@article{32c1233c2f6446bc9d801b572851c31e,
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.",
author = "Diep, {Cuong Q.} and Dongdong Ma and Deo, {Rahul C.} and Holm, {Teresa M.} and Naylor, {Richard W.} and Natasha Arora and Wingert, {Rebecca A.} and Frank Bollig and Gordana Djordjevic and Benjamin Lichman and Hao Zhu and Takanori Ikenaga and Fumihito Ono and Christoph Englert and Cowan, {Chad A.} and Hukriede, {Neil A.} and Handin, {Robert I.} and Davidson, {Alan J.}",
year = "2011",
month = "2",
day = "3",
doi = "10.1038/nature09669",
language = "English (US)",
volume = "470",
pages = "95--101",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7332",

}

TY - JOUR

T1 - Identification of adult nephron progenitors capable of kidney regeneration in zebrafish

AU - Diep, Cuong Q.

AU - Ma, Dongdong

AU - Deo, Rahul C.

AU - Holm, Teresa M.

AU - Naylor, Richard W.

AU - Arora, Natasha

AU - Wingert, Rebecca A.

AU - Bollig, Frank

AU - Djordjevic, Gordana

AU - Lichman, Benjamin

AU - Zhu, Hao

AU - Ikenaga, Takanori

AU - Ono, Fumihito

AU - Englert, Christoph

AU - Cowan, Chad A.

AU - Hukriede, Neil A.

AU - Handin, Robert I.

AU - Davidson, Alan J.

PY - 2011/2/3

Y1 - 2011/2/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79551683930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551683930&partnerID=8YFLogxK

U2 - 10.1038/nature09669

DO - 10.1038/nature09669

M3 - Article

C2 - 21270795

AN - SCOPUS:79551683930

VL - 470

SP - 95

EP - 101

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7332

ER -