Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells

Chang Liu; Ran Wang; Zhisong He; Pierre Osteil; Emilie Wilkie; Xianfa Yang; Jun Chen; Guizhong Cui; Wenke Guo; Yingying Chen; Guangdun Peng; Patrick P.L. Tam; Naihe Jing

Stem Cell Reports (Jul 2018)

Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells

Chang Liu,
Ran Wang,
Zhisong He,
Pierre Osteil,
Emilie Wilkie,
Xianfa Yang,
Jun Chen,
Guizhong Cui,
Wenke Guo,
Yingying Chen,
Guangdun Peng,
Patrick P.L. Tam,
Naihe Jing

Affiliations

Chang Liu: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
Ran Wang: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
Zhisong He: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China
Pierre Osteil: Embryology Unit, Children's Medical Research Institute, Westmead, NSW 2145, Australia
Emilie Wilkie: Embryology Unit, Children's Medical Research Institute, Westmead, NSW 2145, Australia; Bioinformatics Group, Children's Medical Research Institute, Westmead, NSW 2145, Australia
Xianfa Yang: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China
Jun Chen: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
Guizhong Cui: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
Wenke Guo: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China
Yingying Chen: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China
Guangdun Peng: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
Patrick P.L. Tam: Embryology Unit, Children's Medical Research Institute, Westmead, NSW 2145, Australia; School of Medical Sciences, Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia
Naihe Jing: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China; Corresponding author

Journal volume & issue: Vol. 11, no. 1
pp. 43 – 57

Abstract

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Summary: The molecular mechanism underpinning the specification of the ectoderm, a transient germ-layer tissue, during mouse gastrulation was examined here in a stem cell-based model. We captured a self-renewing cell population with enhanced ectoderm potency from mouse epiblast stem cells (EpiSCs) by suppressing Nodal signaling activity. The transcriptome of the Nodal-inhibited EpiSCs resembles that of the anterior epiblast of embryonic day (E)7.0 and E7.5 mouse embryo, which is accompanied by chromatin modifications that reflect the priming of ectoderm lineage-related genes for expression. Nodal-inhibited EpiSCs show enhanced ectoderm differentiation in vitro and contribute to the neuroectoderm and the surface ectoderm in postimplantation chimeras but lose the propensity for mesendoderm differentiation in vitro and in chimeras. Our findings show that specification of the ectoderm progenitors is enhanced by the repression of Nodal signaling activity, and the ectoderm-like stem cells provide an experimental model to investigate the molecular characters of the epiblast-derived ectoderm. : In this article, Liu and colleagues show that Nodal-inhibited epiblast stem cells can self-renew in vitro and display similar transcriptome compared with the ectoderm of late-gastrula embryo. Further analysis shows that inhibition of Nodal signaling predisposes the epigenome to ectoderm-associated status. Moreover, these Nodal-inhibited epiblast stem cells efficiently differentiate to ectodermal cells but not mesendoderm lineages. Keywords: nodal signaling, epiblast stem cells, transcriptome, histone modification, ectoderm propensity

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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