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

doi:10.1016/j.stemcr.2018.05.019

Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells

Stem Cell Reports. 2018 Jul 10;11(1):43-57. doi: 10.1016/j.stemcr.2018.05.019. Epub 2018 Jun 28.

Authors

Chang Liu¹, Ran Wang¹, Zhisong He², Pierre Osteil³, Emilie Wilkie⁴, Xianfa Yang⁵, Jun Chen¹, Guizhong Cui¹, Wenke Guo⁵, Yingying Chen⁵, Guangdun Peng¹, Patrick P L Tam⁶, Naihe Jing⁷

Affiliations

¹ 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.
² CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China.
³ Embryology Unit, Children's Medical Research Institute, Westmead, NSW 2145, Australia.
⁴ Embryology Unit, Children's Medical Research Institute, Westmead, NSW 2145, Australia; Bioinformatics Group, Children's Medical Research Institute, Westmead, NSW 2145, Australia.
⁵ 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.
⁶ 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.
⁷ 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. Electronic address: njing@sibcb.ac.cn.

Abstract

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.

Keywords: ectoderm propensity; epiblast stem cells; histone modification; nodal signaling; transcriptome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Cell Differentiation*
Cell Lineage
Cells, Cultured
Ectoderm / cytology*
Ectoderm / embryology
Ectoderm / metabolism*
Embryonic Development / genetics
Epigenesis, Genetic
Fluorescent Antibody Technique
Gene Expression Profiling
Gene Expression Regulation, Developmental
Germ Layers / cytology*
Germ Layers / metabolism*
Mice
Nodal Protein / metabolism*
Signal Transduction*
Wnt Signaling Pathway

Substances

Biomarkers
Nodal Protein