Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids

Susanne C. van den Brink (), Anna Alemany, Vincent van Batenburg, Naomi Moris, Marloes Blotenburg, Judith Vivié, Peter Baillie-Johnson, Jennifer Nichols, Katharina F. Sonnen, Alfonso Martinez Arias and Alexander van Oudenaarden ()
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Susanne C. van den Brink: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Anna Alemany: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Vincent van Batenburg: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Naomi Moris: University of Cambridge
Marloes Blotenburg: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Judith Vivié: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Peter Baillie-Johnson: University of Cambridge
Jennifer Nichols: University of Cambridge
Katharina F. Sonnen: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
Alfonso Martinez Arias: University of Cambridge
Alexander van Oudenaarden: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht

Nature, 2020, vol. 582, issue 7812, 405-409

Abstract: Abstract Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization1–3. To date, the expression pattern of only a small number of genes in gastruloids has been explored with microscopy, and the extent to which genome-wide expression patterns in gastruloids mimic those in embryos is unclear. Here we compare mouse gastruloids with mouse embryos using single-cell RNA sequencing and spatial transcriptomics. We identify various embryonic cell types that were not previously known to be present in gastruloids, and show that key regulators of somitogenesis are expressed similarly between embryos and gastruloids. Using live imaging, we show that the somitogenesis clock is active in gastruloids and has dynamics that resemble those in vivo. Because gastruloids can be grown in large quantities, we performed a small screen that revealed how reduced FGF signalling induces a short-tail phenotype in embryos. Finally, we demonstrate that embedding in Matrigel induces gastruloids to generate somites with the correct rostral–caudal patterning, which appear sequentially in an anterior-to-posterior direction over time. This study thus shows the power of gastruloids as a model system for exploring development and somitogenesis in vitro in a high-throughput manner.

Date: 2020
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DOI: 10.1038/s41586-020-2024-3

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