转录因子Sall4在ES细胞和iPS细胞中高水平地表达，它是Spalt（sal）家族成员具有典型的C2H2双锌指结构。人SALL4基因的突变可引起常染色体显性遗传性疾病Okihiro综合症。我们前期的研究成果表明，Sall4蛋白具有DNA甲基化和羟甲基化结合活性；在受精卵中特异性地富集于雌雄原核内；其表达抑制可致ES细胞分化；而在体细胞重编程中，Sall4过表达可显著提高iPS效率。由此，我们推测Sall4在早期胚胎发育和体细胞重编程中扮演着重要角色。本课题拟通过CRISPR/Cas9技术建立Sall4条件性敲除小鼠模型，探索Sall4是否参与雄原核去甲基化并揭示其在早期胚胎发育中的作用。此外，我们将以体细胞重编程为研究平台，从基因表达、表观遗传和分化潜能等方面，揭示Sall4在细胞多能性建立和干细胞调控网络中的作用机制，为推进胚胎干细胞和诱导型重编程技术的临床应用提供理论基础。

Transcription factor Sall4, a member of the spalt (sal) gene family which encode proteins characterized by multiple double zinc finger motifs of the C2H2 type, is highly expressed both in the ES cells and iPS cells. Mutations in human SALL4 cause an autosomal dominant disorder known as Okihiro syndrome. Our preliminary data indicate that Sall4 has the DNA methylation/hydroxymethylation binding activity and is specifically enriched both in the male and female pronuclei in the fertilized egg. In the ES cells, depletion of Sall4 by shRNA induces ES cells differentiation. However, Sall4 overexpression during reprogramming can significantly improve the efficiency of iPS generation. Thus, we speculate that Sall4 must play an important role both in the early embryonic development and somatic cell reprogramming. In this project, we intend to generate Sall4 conditional knockout mice by CRISPR/Cas9 system to explore whether Sall4 involves in the active DNA demethylation of male pronucleus and to uncover its role in the early embryonic development. Moreover, through the somatic cell reprogramming system, we will reveal the functions of Sall4 in the establishment and maintenance of pluripotency via gene expression, epigenetic landscape and in vivo/in vitro differentiation potential analysis, thus providing a theoretical basis for the clinical application of embryonic stem cells and iPS cells.