胚胎干细胞具有自我复制和分化成不同类型细胞的特点，研究其分子机理是其安全应用的前提。BAF复合物利用其ATP酶亚基水解ATP产生的能量改变组蛋白与DNA的作用，从而调控基因表达。BAF复合物通过变换亚基组成参入干细胞自我复制和分化的功能。作为BAF复合物的亚基，BAF45d蛋白能与胚胎干细胞核心因子Oct4作用, 但其在干细胞的功能没有报道。我们研究表明敲除BAF45d导致细胞凋亡，改变细胞周期，显著影响干细胞的自我复制及三胚层分化。本课题将通过敲除干细胞及小鼠研究：1，BAF45d对胚胎干细胞自我复制及分化的影响及机理；2，Oct4及PcG复合物在BAF45d干细胞功能中的作用；3，研究敲除BAF45d对小鼠早期胚胎发育的在体影响,深入了解BAF复合物在胚胎干细胞中的功能及机制。BAF45d敲除或条件性敲除小鼠将为研究其在小鼠不同组织，器管的发育提供动物模型。

Embryonic stem (ES) cells have the unique ability to indefinitely self-renew and differentiate into all cell types under appropriate conditions. To fully understand their molecular mechanisms is the essential prerequisite for the clinical application of the ES cells. BAF (Brg1/Brm-associated factors) complex facilitates or represses the gene expression by changing the chromatin structure using the energy of ATP hydrolysis. The BAF complex consists of multiple subunits, by changing the constitution of which BAF complex plays important roles on the maintenance of the identity of ES cells. BAF45d protein was reported to interact with Oct4, one of the key factors in ES cells. However, no study about the function of BAF45d in ES cells has ever been reported. Our preliminary data shown that the deletion of BAF45d induced the apoptosis and changed the cell cycle. More interestingly, we found that the knockout of BAF45d significantly impaired the differentiation of ES cells to mesoderm and endoderm, but promoted the neuronal-ectoderm differentiation. We will use our established BAF45d conditional knockout ES cells to study the functions and their mechanisms in ES cells. Furthermore, we will study the functions of BAF45d on the early embryonic development with the knockout mice.