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

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• 作者：Hila Barak¹ ; ¹¹ ; Sung-Ho Huh¹ ; ¹¹ ; Shuang Chen¹ ; Cé ; cile Jeanpierre³ ; ⁴ ; ⁹ ; Jelena Martinovic¹⁰ ; Mé ; lanie Parisot³ ; ⁴ ; Christine Bole-Feysot⁵ ; Patrick Nitschké ; ⁴ ; ⁶ ; Ré ; mi Salomon³ ; ⁴ ; ⁷ ; ⁹ ; Corinne Antignac³ ; ⁴ ; ⁸ ; ⁹ ; David  ; M. Ornitz¹ ; ^{dornitz@wustl.edu} ; Raphael Kopan¹ ; ² ; ^{kopan@wustl.edu}
• 刊名：Developmental Cell
• 出版年：2012
• 期刊代码：10_15345807
• 类别：bio
• 出版时间：12 June, 2012
• 卷：22
• 期：6
• 页码：1191-1207
• 文件大小：4548 K

摘要

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Summary

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聽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聽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聽vitro.