The Hippo pathway plays a crucial role in cell proliferation and apoptosis and can regulate stem cell maintenance and embryonic development. MOB kinase activators 1A and 1B (Mob1a/b) are key components of the Hippo pathway, whose homozygous deletion in mice causes early embryonic lethality at the preimplantation stage. To investigate the role of Mob1a/b in stem cell maintenance and differentiation, an embryonic stem cell (ESC) clone in which Mob1a/b could be conditionally depleted was generated and characterized. Although Mob1a/b depletion did not affect the stemness or proliferation of mouse ESCs, this depletion caused defects in differentiation into the three germ layers. Yap knockdown rescued the in vitro and in vivo defects in differentiation caused by Mob1a/b depletion, suggesting that differentiation defects caused by Mob1a/b depletion were Yap-dependent. In teratoma experiments, Yap knockdown in Mob1a/b-depleted ESCs partially restored defects in differentiation, indicating that hyperactivation of Taz, another effector of the Hippo pathway, inhibited differentiation into the three germ layers. Taken together, these results suggest that Mob1a/b or Hippo signaling plays a critical role in the differentiation of mouse ESCs into the three germ layers, which is dependent on Yap. These close relationship of the Hippo pathway with the differentiation of stem cells supports its potential as a therapeutic target in regenerative medicine.

Hippo通路在细胞增殖和凋亡中起着至关重要的作用，可以调节干细胞维持和胚胎发育。MOB 激酶激活剂 1A 和 1B (Mob1a/b) 是 Hippo 通路的关键组成部分，其在小鼠中的纯合缺失导致植入前阶段的早期胚胎致死率。为了研究 Mob1a/b 在干细胞维持和分化中的作用，生成并表征了 Mob1a/b 可以有条件地耗尽的胚胎干细胞 (ESC) 克隆。虽然 Mob1a/b 的消耗不影响小鼠 ESC 的干性或增殖，但这种消耗导致分化为三个胚层的缺陷。Yap 敲除挽救了由 Mob1a/b 消耗引起的体外和体内分化缺陷，表明由 Mob1a/b 消耗引起的分化缺陷是 Yap 依赖性的。在畸胎瘤实验中，Mob1a/b 耗尽的 ESC 中的 Yap 敲低部分恢复了分化缺陷，表明 Hippo 通路的另一个效应子 Taz 的过度激活抑制了向三个胚层的分化。总之，这些结果表明 Mob1a/b 或 Hippo 信号传导在小鼠 ESC 分化为依赖于 Yap 的三个胚层中起关键作用。Hippo 通路与干细胞分化的密切关系支持其作为再生医学治疗靶点的潜力。Hippo 通路的另一个效应子抑制了向三个胚层的分化。总之，这些结果表明 Mob1a/b 或 Hippo 信号传导在小鼠 ESC 分化为依赖于 Yap 的三个胚层中起关键作用。Hippo 通路与干细胞分化的密切关系支持其作为再生医学治疗靶点的潜力。Hippo 通路的另一个效应子抑制了向三个胚层的分化。总之，这些结果表明 Mob1a/b 或 Hippo 信号传导在小鼠 ESC 分化为依赖于 Yap 的三个胚层中起关键作用。Hippo 通路与干细胞分化的密切关系支持其作为再生医学治疗靶点的潜力。