title: Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yongshun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Willis
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA.
authors.forename: Guokai
authors.initials: G
authors.lastname: Chen
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D054262:Gastrulation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039904:Pluripotent Stem Cells / Q000502:physiology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology
chemical_list: C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins