Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids.
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van Batenburg, Vincent
Martinez Arias, Alfonso
van Oudenaarden, Alexander
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van den Brink, S. C., Alemany, A., van Batenburg, V., Moris, N., Blotenburg, M., Vivié, J., Baillie-Johnson, P., et al. (2020). Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids.. Nature, 582 (7812), 405-409. https://doi.org/10.1038/s41586-020-2024-3
Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization1,2,3. 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.
Organoids, Gastrula, Somites, Animals, Mice, Collagen, Proteoglycans, Laminin, Drug Combinations, Gene Expression Regulation, Developmental, Embryonic Development, Time Factors, Female, Male, Embryo, Mammalian, Single-Cell Analysis, Transcriptome, Mouse Embryonic Stem Cells, RNA-Seq
This work was supported by an European Research Council Advanced grant (ERC-AdG 742225-IntScOmics), a Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP award (NWOCW 714.016.001), and the Foundation for Fundamental Research on Matter, financially supported by NWO (FOM-14NOISE01) to S.C.v.d.B., A.A., V.v.B., M.B., J.V. and A.v.O., a BBSRC (No. BB/M023370/1 and BB/P003184/1), Newton Trust (INT16.24b) and MRC (MR/R017190/1) grant to A.M.A., a Newnham College Cambridge Junior Research Fellowship to N.M., and a studentship from the Engineering and Physical Sciences Research Council (EPSRC) to P.B.J.. The Cambridge Stem Cell Institute is supported by core funding from the Wellcome Trust and Medical Research Council; J. N. was funded by the University of Cambridge, and K.F.S. by core funding from the Hubrecht Institute. This work is part of the Oncode Institute which is partly financed by the Dutch Cancer Society.
WELLCOME TRUST (105031/D/14/Z)
External DOI: https://doi.org/10.1038/s41586-020-2024-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/298148
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