FGF9 and FGF20 Maintain the Stemness of Nephron Progenitors in Mice and Man

Hila Barak, Sung Ho Huh, Shuang Chen, Cécile Jeanpierre, Jelena Martinovic, Mélanie Parisot, Christine Bole-Feysot, Patrick Nitschké, Rémi Salomon, Corinne Antignac, David M. Ornitz, Raphael Kopan

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

The identity of niche signals necessary to maintain embryonic nephron progenitors is unclear. Here we provide evidence that Fgf20 and Fgf9, expressed in the niche, and Fgf9, secreted from the adjacent ureteric bud, are necessary and sufficient to maintain progenitor stemness. Reduction in the level of these redundant ligands in the mouse led to premature progenitor differentiation within the niche. Loss of FGF20 in humans, or of both ligands in mice, resulted in kidney agenesis. Sufficiency was shown in vitro where Fgf20 or Fgf9 (alone or together with Bmp7) maintained isolated metanephric mesenchyme or sorted nephron progenitors that remained competent to differentiate in response to Wnt signals after 5 or 2 days in culture, respectively. These findings identify a long-sought-after critical component of the nephron stem cell niche and hold promise for long-term culture and utilization of these progenitors in vitro.

Original languageEnglish (US)
Pages (from-to)1191-1207
Number of pages17
JournalDevelopmental cell
Volume22
Issue number6
DOIs
StatePublished - Jun 12 2012

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Nephrons
Ligands
Stem cells
Stem Cell Niche
Mesoderm
Kidney
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Barak, H., Huh, S. H., Chen, S., Jeanpierre, C., Martinovic, J., Parisot, M., ... Kopan, R. (2012). FGF9 and FGF20 Maintain the Stemness of Nephron Progenitors in Mice and Man. Developmental cell, 22(6), 1191-1207. https://doi.org/10.1016/j.devcel.2012.04.018

FGF9 and FGF20 Maintain the Stemness of Nephron Progenitors in Mice and Man. / Barak, Hila; Huh, Sung Ho; Chen, Shuang; Jeanpierre, Cécile; Martinovic, Jelena; Parisot, Mélanie; Bole-Feysot, Christine; Nitschké, Patrick; Salomon, Rémi; Antignac, Corinne; Ornitz, David M.; Kopan, Raphael.

In: Developmental cell, Vol. 22, No. 6, 12.06.2012, p. 1191-1207.

Research output: Contribution to journalArticle

Barak, H, Huh, SH, Chen, S, Jeanpierre, C, Martinovic, J, Parisot, M, Bole-Feysot, C, Nitschké, P, Salomon, R, Antignac, C, Ornitz, DM & Kopan, R 2012, 'FGF9 and FGF20 Maintain the Stemness of Nephron Progenitors in Mice and Man', Developmental cell, vol. 22, no. 6, pp. 1191-1207. https://doi.org/10.1016/j.devcel.2012.04.018
Barak, Hila ; Huh, Sung Ho ; Chen, Shuang ; Jeanpierre, Cécile ; Martinovic, Jelena ; Parisot, Mélanie ; Bole-Feysot, Christine ; Nitschké, Patrick ; Salomon, Rémi ; Antignac, Corinne ; Ornitz, David M. ; Kopan, Raphael. / FGF9 and FGF20 Maintain the Stemness of Nephron Progenitors in Mice and Man. In: Developmental cell. 2012 ; Vol. 22, No. 6. pp. 1191-1207.
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