基于多组学技术解析猪皮肤干细胞转分化原始生殖细胞的表观遗传学调控机制

最近研究表明DNA甲基化、组蛋白修饰以及非编码RNA等表观遗传修饰调控在体细胞重编程、干细胞分化等细胞命运决定过程中起着重要作用。皮肤来源干细胞(SDSCs)是一种易获得且具有向生殖细胞分化潜能的成体干细胞。目前尚无关于表观遗传修饰调控猪SDSCs(pSDSCs)转分化为原始生殖细胞样细胞(PGCLCs)的报道。本课题拟在已完成基金项目的基础上，即已确定pSDSCs转分化为pPGCLCs必须经历pSDSCs向外胚层样细胞(EpiLCs)去分化和EpiLCs向PGCLCs再分化两个连续的、不同的分化阶段，采用组学技术如WGBS、ChIP-seq、RNA-seq等，分析表观遗传修饰在pSDSCs转分化为pPGCLCs不同分化阶段的影响，研究调控表观遗传学修饰改变的具体分子机制。该项目将深入探索干细胞分化为生殖细胞的调节机制，为动物干细胞和繁殖生物技术研究提供理论依据和技术支持。

Stem cells are undifferentiated progenitor cells that play an important role as a source of seed cells during tissue regeneration and as a model to investigate the lineage-specification. Outstanding research in recent years has shed light on the role of the epigenetic modifications in stem cell. Studies have indicated that epigenetic modifications such as DNA methylation, histone modification and non-coding RNA are important stem cells self-renewal and differentiation and somatic cell reprogram. Furthermore, a critical role for epigenetic modifications in controlling self-renewal, differentiation, aging and apoptosis of stem cells has also been revealed. The epigenetic modifications can regulate cell shape and affect cell fate determination. However, how these epigenetic modifications are transduced to regulate biological processes in the cells has remained elusive. The objective of this project is to elucidate a novel mechanism through which the interactions between epigenetic modifications and porcine skin-derived stem cells (SDSCs) transdifferentiation. Such mechanisms may explain how epigenetic modifications regulate cellular behavior and determine cell fate.