title: Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling.
abstract: The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development. Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation. Here, we demonstrate that through brief inhibition of Nodal signaling in vitro, mouse embryonic stem cell (ESC)-derived epiblast stem cells (ESD-EpiSCs) could be committed to transient ectodermal progenitor populations, which possess the ability to give rise to neural or epidermal ectoderm in the absence or presence of BMP4, respectively. Mechanistic studies reveal that BMP4 recruits distinct transcriptional targets in ESD-EpiSCs and ectoderm-like cells. Furthermore, FGF-Erk signaling may also be alleviated during the generation of ectoderm-like cells. Thus, our data suggest that instructive interactions among several extracellular signals participate in the commitment of ectoderm from ESD-EpiSCs, which shed new light on the understanding of the formation of ectoderm during the gastrulation in early mouse embryo development.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Present address: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Guangdun
authors.initials: G
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Pingyu
authors.initials: P
authors.lastname: Liu
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang 330031, Jiangxi, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, ON M5G 1X8, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China njing@sibcb.ac.cn.
authors.forename: Naihe
authors.initials: N
authors.lastname: Jing
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004475:Ectoderm / Q000166:cytology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D005855:Germ Layers / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055457:Nodal Protein
keywords: BMP4; EpiSCs; FGF; Nodal; ectoderm