Abstract：
Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.
摘要：
胚胎干细胞(ESC)可以分化成胚胎胚层的所有细胞类型。ESC还可以产生全能2C样细胞和滋养外胚层细胞。然而,由于表观遗传障碍，这些后一种转变以低频率发生，其性质尚未完全理解。这里,我们表明,用丁酸钠(NaB)处理小鼠ESCs可增加2C样细胞的数量,并可将ESCs直接重编程为滋养干细胞(TSCs),而不会转变为2C样状态.机械上,NaB抑制LSD1-HDAC1/2共阻遏复合物中的组蛋白脱乙酰酶活性。这增加了2C-和TSC-特异性基因调节区的乙酰化水平，促进他们的表达。此外,NaB处理的细胞获得产生胚泡样结构的能力，该结构可以在体外发育超过植入阶段并在体内形成蜕膜。这些结果确定了表观遗传学如何限制小鼠ESC中的全能性和滋养外胚层命运。
