The role of p53 dependent and cooperating pathways in pluripotency induction

体细胞重编程成诱导多能干细胞（iPS cells）可以作为一个实验系统来理解干细胞生物学的基本机制，包括促进或限制多能性的机制。先前的研究表明，p53缺失可以强烈增加iPS的形成，也可以增强成体干细胞的自我更新。控制多能性的P53依赖机制仍有待确定。利用iPS系统、遗传小鼠模型和慢病毒shRNA文库，我们将专注于以下主要目标：(i)确定p53依赖的DNA损伤检查点在多能诱导中的作用，（ii）确定p53是否有助于多能途径的调控，（iii）确定多能诱导过程中与p53合作的途径。该项目将增加我们对多能性诱导的理解，特别是p53依赖机制在这一过程中的作用。

Reprogramming of somatic cells into induced pluripotent stem cells (iPS cells) can serve as an experimental system to understand basic mechanisms in stem cell biology, including mechanisms that facilitate or restrict pluripotency. Previous studies have shown that p53 deletion can strongly increase iPS formation and can also enhance the self-renewal of adult stem cells. p53 dependent mechanisms that control pluripotency remain yet to be defined. Using the iPS system, genetic mouse models and lentiviral shRNA libraries we will focus on following main aims: (i) Define the role of p53 dependent DNA damage checkpoints in pluripotency induction, (ii) Determine whether p53 contributes to the regulation of pluripotency pathways, (iii) Identify pathways that cooperate with p53 during pluripotency induction. The project will increase our understanding of pluripotency induction, specifically the role of p53 dependent mechanisms in this process.