Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre

Peng-Fei Xu, Ricardo Moraes Borges, Jonathan Fillatre, Maraysa Oliveira-Melo, Tao Cheng, Bernard Thisse and Christine Thisse ()
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Peng-Fei Xu: University of Virginia
Ricardo Moraes Borges: University of Virginia
Jonathan Fillatre: University of Virginia
Maraysa Oliveira-Melo: University of Virginia
Tao Cheng: Zhejiang University
Bernard Thisse: University of Virginia
Christine Thisse: University of Virginia

Nature Communications, 2021, vol. 12, issue 1, 1-22

Abstract: Abstract Generating properly differentiated embryonic structures in vitro from pluripotent stem cells remains a challenge. Here we show that instruction of aggregates of mouse embryonic stem cells with an experimentally engineered morphogen signalling centre, that functions as an organizer, results in the development of embryo-like entities (embryoids). In situ hybridization, immunolabelling, cell tracking and transcriptomic analyses show that these embryoids form the three germ layers through a gastrulation process and that they exhibit a wide range of developmental structures, highly similar to neurula-stage mouse embryos. Embryoids are organized around an axial chordamesoderm, with a dorsal neural plate that displays histological properties similar to the murine embryo neuroepithelium and that folds into a neural tube patterned antero-posteriorly from the posterior midbrain to the tip of the tail. Lateral to the chordamesoderm, embryoids display somitic and intermediate mesoderm, with beating cardiac tissue anteriorly and formation of a vasculature network. Ventrally, embryoids differentiate a primitive gut tube, which is patterned both antero-posteriorly and dorso-ventrally. Altogether, embryoids provide an in vitro model of mammalian embryo that displays extensive development of germ layer derivatives and that promises to be a powerful tool for in vitro studies and disease modelling.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23653-4

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DOI: 10.1038/s41467-021-23653-4

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