Journal Article

Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro

Harrison, Sarah Ellys, Sozen, Berna, Kyprianou, Christos, Zernicka-Goetz, Magdalena, Christodoulou, Neophytos

2017

Overview

Pluripotent embryonic stem cells (ESCs) can differentiate into any adult cell type; however, aggregates of these cells do not mimic embryonic architecture when grown in culture. To see whether mouse ESCs and their extraembryonic counterparts, trophoblast stem cells (TSCs), can recapitulate normal development, Harrison et al. combined ESCs and TSCs in an extracellular matrix culture (see the Perspective by Pera). The resultant “ETS-embryos” displayed considerable resemblance to normal embryos, even specifying mesoderm and primordial germ cells at the boundary between embryonic and extraembryonic compartments. These ETS-embryos are a genetically tractable tool for studying mammalian embryogenesis. Science , this issue p. eaal1810 ; see also p. 137 Embryonic and trophoblast stem cells self-assemble to generate a structure resembling a natural mouse embryo. Mammalian embryogenesis requires intricate interactions between embryonic and extraembryonic tissues to orchestrate and coordinate morphogenesis with changes in developmental potential. Here, we combined mouse embryonic stem cells (ESCs) and extraembryonic trophoblast stem cells (TSCs) in a three-dimensional scaffold to generate structures whose morphogenesis is markedly similar to that of natural embryos. By using genetically modified stem cells and specific inhibitors, we show that embryogenesis of ESC- and TSC-derived embryos—ETS-embryos—depends on cross-talk involving Nodal signaling. When ETS-embryos develop, they spontaneously initiate expression of mesoderm and primordial germ cell markers asymmetrically on the embryonic and extraembryonic border, in response to Wnt and BMP signaling. Our study demonstrates the ability of distinct stem cell types to self-assemble in vitro to generate embryos whose morphogenesis, architecture, and constituent cell types resemble those of natural embryos.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adults / Animal models / Animals / Architecture / Basements / Bone morphogenetic proteins / Boundaries / Cavitation / Cell culture / Compartments / Construction / Crosstalk / Culture / Developmental stages / Ectoderm / Embryo cells / Embryo Implantation / Embryo, Mammalian - cytology / Embryo, Mammalian - physiology / Embryogenesis / Embryology / Embryonic Development / Embryonic growth stage / Embryonic Stem Cells - physiology / Embryos / Endoderm / Extracellular matrix / Gastrulation / Genetic modification / Germ cells / Germ Layers / Holes / In Vitro Techniques / In vitro testing / Mammals / Markers / Membranes / Mesoderm / Mesoderm - cytology / Mesoderm - growth & development / Mice / Models, Biological / Molecular modelling / Morphogenesis / Oct-4 protein / Partnerships / Pattern formation / Placenta / Pluripotency / Polarization / RESEARCH ARTICLE SUMMARY / Scaffolds / Self-assembly / Signaling / Specifications / Stem cells / Tissue Scaffolds / Trophoblasts - physiology / Wnt Signaling Pathway / Yolk