Lin Yongshun, Li Xiao-Yan, Willis Amanda L, Liu Chengyu, Chen Guokai, Weiss Stephen J
1] Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA [2] Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA.
Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nat Commun. 2014;5:3070. doi: 10.1038/ncomms4070.
Embryonic stem cells (ESCs) exhibit the dual properties of self-renewal and pluripotency as well as the ability to undergo differentiation that gives rise to all three germ layers. Wnt family members can both promote ESC maintenance and trigger differentiation while also controlling the expression of Snail1, a zinc-finger transcriptional repressor. Snail1 has been linked to events ranging from cell cycle regulation and cell survival to epithelial-mesenchymal transition (EMT) and gastrulation, but its role in self-renewal, pluripotency or lineage commitment in ESCs remains undefined. Here we demonstrate using isogenic pairs of conditional knockout mouse ESCs, that Snail1 exerts Wnt- and EMT independent control over the stem cell transcriptome without affecting self-renewal or pluripotency-associated functions. By contrast, during ESC differentiation, an endogenous Wnt-mediated burst in Snail1 expression regulates neuroectodermal fate while playing a required role in epiblast stem cell exit and the consequent lineage fate decisions that define mesoderm commitment.
胚胎干细胞（ESC）具有自我更新和多能性的双重特性，以及进行分化产生所有三个胚层的能力。Wnt家族成员既能促进ESC的维持，触发分化，同时还能控制锌指转录抑制因子Snail1的表达。Snail1与从细胞周期调控、细胞存活到上皮-间质转化（EMT）和原肠胚形成等一系列事件相关，但它在ESC的自我更新、多能性或谱系定向中的作用仍不明确。在这里，我们使用条件性敲除小鼠ESC的同基因对进行证明，Snail1对干细胞转录组发挥独立于Wnt和EMT的控制作用，而不影响自我更新或多能性相关功能。相比之下，在ESC分化过程中，内源性Wnt介导的Snail1表达爆发调节神经外胚层命运，同时在胚泡干细胞退出以及随后决定中胚层定向的谱系命运决定中发挥必要作用。
