DPPA2 and DPPA4 are dispensable for mouse zygotic genome activation and preimplantation development

How maternal factors in oocytes initiate zygotic genome activation (ZGA) remains elusive. Recent studies indicate that DPPA2 and DPPA4 are required for establishing a 2-cell embryo-like (2C-like) state in mouse embryonic stem cells (ESCs) in a DUX-dependent manner. These results suggest that DPPA2 and DPPA4 are essential maternal factors that regulate Dux and ZGA in embryos. By analyzing maternal knockout and maternal-zygotic knockout embryos, we unexpectedly found that Dux activation, ZGA, and preimplantation development are normal in embryos without DPPA2 or DPPA4. Thus, unlike in ESCs/2C-like cells, DPPA2 and DPPA4 are dispensable for ZGA and preimplantation development. Comparison of WT and mutant Dppa2/4 1-cell and 2-cell embryo transcriptome卵母细胞（oocytes）中的母源因子（maternal factors）如何启动合子基因组激活（zygotic genome activation, ZGA），这一问题至今仍未阐明。近期研究表明，在小鼠胚胎干细胞（ESCs）中，DPPA2与DPPA4以依赖DUX的方式，对建立二细胞胚胎样（2C-like）状态不可或缺。上述结果提示，DPPA2与DPPA4是调控胚胎中Dux表达与合子基因组激活的关键母源因子。本研究通过分析母源敲除（maternal knockout）及母源-合子敲除（maternal-zygotic knockout）胚胎，意外发现：在缺失DPPA2或DPPA4的胚胎中，Dux激活、合子基因组激活以及着床前发育（preimplantation development）均无异常。因此，与胚胎干细胞/2C样细胞中的情况不同，DPPA2与DPPA4对于合子基因组激活和着床前发育并非必需。本研究对野生型（wild type, WT）与Dppa2/4突变型的1细胞及2细胞胚胎转录组（transcriptome）进行了比较。