Show simple item record

dc.contributor.authorvan den Brink, Susanne Cen
dc.contributor.authorAlemany, Annaen
dc.contributor.authorvan Batenburg, Vincenten
dc.contributor.authorMoris, Naomien
dc.contributor.authorBlotenburg, Marloesen
dc.contributor.authorVivié, Judithen
dc.contributor.authorBaillie-Johnson, Peteren
dc.contributor.authorNichols, Jenniferen
dc.contributor.authorSonnen, Katharina Fen
dc.contributor.authorMartinez Arias, Alfonsoen
dc.contributor.authorvan Oudenaarden, Alexanderen
dc.date.accessioned2019-10-29T00:31:30Z
dc.date.available2019-10-29T00:31:30Z
dc.date.issued2020-06en
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/298148
dc.description.abstractGastruloids 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.
dc.description.sponsorshipThis 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.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherWithheld
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectOrganoidsen
dc.subjectGastrulaen
dc.subjectSomitesen
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectCollagenen
dc.subjectProteoglycansen
dc.subjectLamininen
dc.subjectDrug Combinationsen
dc.subjectGene Expression Regulation, Developmentalen
dc.subjectEmbryonic Developmenten
dc.subjectTime Factorsen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectEmbryo, Mammalianen
dc.subjectSingle-Cell Analysisen
dc.subjectTranscriptomeen
dc.subjectMouse Embryonic Stem Cellsen
dc.subjectRNA-Seqen
dc.titleSingle-cell and spatial transcriptomics reveal somitogenesis in gastruloids.en
dc.typeArticle
prism.endingPage409
prism.issueIdentifier7812en
prism.publicationDate2020en
prism.publicationNameNatureen
prism.startingPage405
prism.volume582en
dc.identifier.doi10.17863/CAM.45205
dcterms.dateAccepted2019-12-19en
rioxxterms.versionofrecord10.1038/s41586-020-2024-3en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-06en
dc.contributor.orcidvan den Brink, Susanne C [0000-0003-3683-7737]
dc.contributor.orcidMoris, Naomi [0000-0003-1910-5454]
dc.contributor.orcidBaillie-Johnson, Peter [0000-0003-2157-5017]
dc.contributor.orcidNichols, Jennifer [0000-0002-8650-1388]
dc.contributor.orcidSonnen, Katharina F [0000-0002-2902-9419]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (105031/D/14/Z)
pubs.funder-project-idEPSRC (1359454)
pubs.funder-project-idEPSRC (EP/K503009/1)
pubs.funder-project-idEPSRC (EP/L504920/1)
pubs.funder-project-idMRC (MR/R017190/1)
pubs.funder-project-idBBSRC (BB/M004023/1)
pubs.funder-project-idBBSRC (BB/P003184/1)
pubs.funder-project-idBBSRC (BB/S001816/1)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
cam.orpheus.successTue Mar 31 10:39:00 BST 2020 - Embargo updated*
cam.orpheus.counter2*
rioxxterms.freetoread.startdate2020-08-19


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record