Mouse embryonic stem cells (ESCs) cultured in defined medium resemble the pre-implantation epiblast in the ground state, with full developmental capacity including the germline. β-Catenin is required to maintain ground state pluripotency in mouse ESCs, but its exact role is controversial. Here, we reveal a Tcf3-independent role of β-catenin in restraining germline and somatic lineage differentiation genes. We show that β-catenin binds target genes with E2F6 and forms a complex with E2F6 and HMGA2 or E2F6 and HP1γ. Our data indicate that these complexes help β-catenin restrain and fine-tune germ cell and neural developmental potential. Overall, our data reveal a previously unappreciated role of β-catenin in preserving lineage differentiation integrity in ground state ESCs.

在确定的培养基中培养的小鼠胚胎干细胞（ESC）与基态的植入前上皮细胞相似，具有包括种系在内的完整发育能力。需要β-连环蛋白来维持小鼠ESC中的基态多能性，但其确切作用尚存争议。在这里，我们揭示了β-连环蛋白在抑制种系和体细胞谱系分化基因中的Tcf3独立作用。我们显示，β-catenin与E2F6结合靶基因，并与E2F6和HMGA2或E2F6和HP1γ形成复合物。我们的数据表明，这些复合物有助于β-连环蛋白抑制并微调生殖细胞和神经发育潜能。总的来说，我们的数据揭示了β-连环蛋白在维持基态ESCs谱系分化完整性中的作用。