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

174 Scopus citations

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

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Identification of adult nephron progenitors capable of kidney regeneration in zebrafish'. Together they form a unique fingerprint.

  • Cite this

    Diep, C. Q., Ma, D., Deo, R. C., Holm, T. M., Naylor, R. W., Arora, N., Wingert, R. A., Bollig, F., Djordjevic, G., Lichman, B., Zhu, H., Ikenaga, T., Ono, F., Englert, C., Cowan, C. A., Hukriede, N. A., Handin, R. I., & 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