YAP是Hippo通路抑制的效应因子,参与多种生理和病理过程。研究显示YAP也调控小鼠胚胎干细胞（ESCs）的分化，但具体机制还不清楚。我们的研究揭示YAP高表达的Hippo 通路阻断的胚胎干细胞Mst-/-ESCs倾向于向外胚层细胞分化，而向中胚层和内胚层细胞的分化受阻。ChIP-seq实验显示YAP在ESCs的超级增强子上高度富集，且在Mst-/-ESCs中，一些YAP富集的调控胚层基因的新超级增强子出现。因此我们推测YAP及其相关的超级增强子共同参与调控小鼠ESCs的倾向性分化。此课题中我们将在ESCs中过表达和敲降YAP，采用ChIP-seq和免疫荧光超分辨成像法研究YAP量变对超级增强子的影响；IP实验研究YAP与其它ESCs超级增强子关联蛋白的关系；通过RNA干扰，研究YAP富集的超级增强子所调控的基因对ESCs分化的影响；综合分析YAP调控小鼠ESCs分化的作用机制。

YAP is the Hippo pathway inhibited effector. It involves in a broad spectrum of physiological and pathological procedure. Previous research showed that YAP also contributes to regulate embryonic stem cell (ESC) differentiation, but the detailed mechanism is not clear yet. Our previous work revealed that YAP is highly expressed in Mst1 and Mst2 knockout (Mst-/-) ESCs, and these cells preferentially differentiate into ectoderm lineage cells, but their differentiation to mesoderm and endoderm lineage cells is disturbed. ChIP-seq assays revealed that YAP is enriched in super-enhancers in ESCs. While in Mst-/- ESCs, some YAP enriched novel super-enhancers that regulate germ lay lineage genes appear. Hence, we deduce that YAP and its associated super-enhancers play a role in regulating mouse ESC lineage preferential differentiation. In this project. We will overexpress and knock down YAP in ESCs, and study the effect of YAP level change on super-enhancers using immunofluorescence microscopy and ChIP-seq; Using IP assays to study the relationship of YAP and other super-enhancer components；Using RNA interference to study the function of YAP associated super-enhancer regulated genes on ESC lineage differentiation。We aim to uncover the mechanism how YAP regulates ESC differentiation.