Mechanisms regulating the maintenance of nephron progenitors

成人肾脏永不再生，但胚胎肾脏含有肾元祖细胞。本研究的目的是揭示胚胎肾元祖细胞维持的分子机制。我们产生了祖细胞特异性和药物诱导的Sall1突变小鼠，发现在Sall1缺失后肾元祖细胞迅速耗尽。我们确定了Sall1的直接下游靶点，发现Sall1在祖细胞中起正调节作用，同时抑制新生肾元分化过程中的异常基因表达。目前，我们正试图利用已获得的信息，建立一种自我更新祖细胞的方法。如果成功，它将成为肾脏再生的基础，因为在正常情况下，肾脏祖细胞在出生后不久就消失了。

The adult kidney never regenerates, but the embryonic kidney contains nephron progenitors. The purpose of this project was to reveal molecular mechanisms underlying the maintenance of the embryonic nephron progenitors. We generated progenitor-specific and drug-inducible Sall1 mutant mice, and found that nephron progenitors were rapidly depleted upon Sall1 deletion. We identified the direct downstream targets of Sall1 and found that Sall1 functions as a positive regulator in the progenitors, while repressing aberrant gene expression in differentiating nascent nephrons. We are currently trying to establish a method to self-renew the progenitors, by utilizing the obtained information. If successful, it would serve as a basis toward kidney regeneration, because the nephron progenitors disappear shortly after birth in a normal condition.