An in vitro model of early anteroposterior organization during human development

Naomi Moris (), Kerim Anlas, Susanne C. van den Brink, Anna Alemany, Julia Schröder, Sabitri Ghimire, Tina Balayo, Alexander van Oudenaarden () and Alfonso Martinez Arias ()
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Naomi Moris: University of Cambridge
Kerim Anlas: University of Cambridge
Susanne C. van den Brink: Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Anna Alemany: Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Julia Schröder: University of Cambridge
Sabitri Ghimire: University of Cambridge
Tina Balayo: University of Cambridge
Alexander van Oudenaarden: Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Alfonso Martinez Arias: University of Cambridge

Nature, 2020, vol. 582, issue 7812, 410-415

Abstract: Abstract The body plan of the mammalian embryo is shaped through the process of gastrulation, an early developmental event that transforms an isotropic group of cells into an ensemble of tissues that is ordered with reference to three orthogonal axes1. Although model organisms have provided much insight into this process, we know very little about gastrulation in humans, owing to the difficulty of obtaining embryos at such early stages of development and the ethical and technical restrictions that limit the feasibility of observing gastrulation ex vivo2. Here we show that human embryonic stem cells can be used to generate gastruloids—three-dimensional multicellular aggregates that differentiate to form derivatives of the three germ layers organized spatiotemporally, without additional extra-embryonic tissues. Human gastruloids undergo elongation along an anteroposterior axis, and we use spatial transcriptomics to show that they exhibit patterned gene expression. This includes a signature of somitogenesis that suggests that 72-h human gastruloids show some features of Carnegie-stage-9 embryos3. Our study represents an experimentally tractable model system to reveal and examine human-specific regulatory processes that occur during axial organization in early development.

Date: 2020
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DOI: 10.1038/s41586-020-2383-9

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