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

被引：232

作者：

Barak, Hila ^{[1
]}

Huh, Sung-Ho ^{[1
]}

Chen, Shuang ^{[1
]}

Jeanpierre, Cecile ^{[3
,4
,7
]}

Martinovic, Jelena ^{[8
,9
]}

Parisot, Melanie ^{[3
,4
]}

Bole-Feysot, Christine

Nitschke, Patrick ^{[4
]}

Salomon, Remi ^{[3
,4
,5
,7
]}

Antignac, Corinne ^{[3
,4
,6
,7
]}

Ornitz, David M. ^{[1
]}

Kopan, Raphael ^{[1
,2
]}

机构：

[1] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[3] Univ Paris 05, INSERM, U983, Paris, France

[4] Univ Paris 05, Inst Imagine, Paris, France

[5] Hop Necker Enfants Malad, AP HP, Dept Pediat Nephrol, F-75015 Paris, France

[6] Hop Necker Enfants Malad, AP HP, Dept Genet, F-75015 Paris, France

[7] Univ Paris 05, F-75006 Paris, France

[8] Hop Antoine Beclere, AP HP, F-92140 Clamart, France

[9] Hop Antoine Beclere, Dept Fetopathol, Lab Cerba, F-92140 Clamart, France

来源：

DEVELOPMENTAL CELL | 2012年 / 22卷 / 06期

关键词：

FIBROBLAST-GROWTH-FACTOR; RECEPTOR SPECIFICITY; MAMMALIAN KIDNEY; MOUSE KIDNEY; CELLS; MESENCHYME; EXPRESSION; NUMBER; GENE; MORPHOGENESIS;

D O I：

10.1016/j.devcel.2012.04.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 sternness. 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.

引用

页码：1191 / 1207

页数：17

共 64 条

[1]

Barak H., 2011, COLD SPRING HARB PRO, V2011

[2]

Ureteric bud cells secrete multiple factors, including bFGF, which rescue renal progenitors from apoptosis [J].