The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK; Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, UK.
Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, UK.
Stem Cell Reports. 2015 Apr 14;4(4):551-60. doi: 10.1016/j.stemcr.2015.01.021. Epub 2015 Mar 5.
Nephron progenitor cells differentiate to form nephrons during embryonic kidney development. In contrast, self-renewal maintains progenitor numbers and premature depletion leads to impaired kidney function. Here we analyze the PI3K pathway as a point of convergence for the multiple pathways that are known to control self-renewal in the kidney. We demonstrate that a reduction in PI3K signaling triggers premature differentiation of the progenitors and activates a differentiation program that precedes the mesenchymal-to-epithelial transition through ectopic activation of the β-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors.
肾祖细胞在胚胎肾发育过程中分化形成肾单位。相比之下，自我更新维持祖细胞数量，而过早耗竭则导致肾功能受损。在这里，我们分析了 PI3K 途径作为已知控制肾脏自我更新的多个途径的交汇点。我们证明，PI3K 信号的减少会触发祖细胞的过早分化，并通过β-catenin 途径的异位激活激活一个先于间充质到上皮转变的分化程序。因此，PI3K 和其他途径的综合输出精细地调整了肾祖细胞中自我更新和分化之间的平衡。
