The epigenetic modifier Fam208a is required to maintain epiblast cell potency

Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid cellular proliferation and extensive epigenetic programming. Here, we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development using mouse strains harbouring two different allelic mutations. We show that at E6.5, Fam208a mutants have a decreased number of Oct4-positive epiblast cells due to an increase in p53-driven apoptosis. Complete removal of p53 could rescue the gastrulation block in Fam208a mutants, enabling them to develop until E8.5-9.0. The data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness thereby, making it an important factor at the onset of gastrulation.原肠胚形成（Gastrulation）以原条（primitive streak）的形成为起始事件，此过程中，上胚层（epiblast）细胞发生分层脱离，进而分化形成中胚层（mesoderm）与定型内胚层（definitive endoderm）。在此阶段，上胚层的多能细胞群会经历极为快速的细胞增殖与广泛的表观遗传编程。本研究通过携带两种不同等位基因突变的小鼠品系，证实新型表观遗传调控因子Fam208a对胚胎植入后早期发育至关重要。研究发现，在胚胎第6.5天（E6.5），Fam208a突变体中因p53介导的细胞凋亡水平升高，导致八聚体结合转录因子4（Oct4）阳性的上胚层细胞数量减少。完全敲除p53可挽救Fam208a突变体的原肠胚形成阻滞，使其能够发育至胚胎第8.5-9.0天（E8.5-9.0）。本研究数据揭示了Fam208a在维持上胚层细胞存活能力中的全新体内功能，使其成为原肠胚形成起始阶段的关键调控因子。