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Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling Free
Lingyu Li1,4,†, Lu Song1,†, Chang Liu1, Jun Chen1, Guangdun Peng1, Ran Wang1, Pingyu Liu1, Ke Tang2, Janet Rossant3, and Naihe Jing1,*
1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2Institute of Life Science, Nanchang University, Nanchang 330031, Jiangxi, China
3Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, ON M5G 1X8, Canada
4Present address: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA *Correspondence to:Naihe Jing, E-mail: njing@sibcb.ac.cn
J Mol Cell Biol, Volume 7, Issue 5, October 2015, 455-465,  https://doi.org/10.1093/jmcb/mjv030
Keyword: EpiSCs, ectoderm, BMP4, Nodal, FGF

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.