Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St. Louis, MO 63110, USA.
Dev Cell. 2012 Jun 12;22(6):1191-207. doi: 10.1016/j.devcel.2012.04.018.
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.
维持胚胎肾祖细胞的龛信号的身份尚不清楚。在这里，我们提供的证据表明，龛中表达的 Fgf20 和 Fgf9 以及从相邻输尿管芽分泌的 Fgf9 是维持祖细胞干性所必需和充分的。在小鼠中这些冗余配体水平的降低导致龛内祖细胞过早分化。人类 FGF20 缺失或小鼠两种配体缺失均导致肾脏发育不全。在体外实验中，Fgf20 或 Fgf9（单独或与 Bmp7 一起）维持分离的后肾间充质或分选的肾祖细胞，在培养 5 或 2 天后，它们仍然能够对 Wnt 信号做出反应而分化。这些发现确定了长期以来寻找的肾祖细胞龛的一个关键组成部分，并为这些祖细胞在体外的长期培养和利用提供了希望。
