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dc.contributor.authorKobayashi, T,en
dc.contributor.authorZhang, H,en
dc.contributor.authorTang, WC,en
dc.contributor.authorIrie, N,en
dc.contributor.authorWithey, S,en
dc.contributor.authorKlisch, D,en
dc.contributor.authorSybirna, A,en
dc.contributor.authorDietmann, S,en
dc.contributor.authorContreras, DA,en
dc.contributor.authorWebb, R,en
dc.contributor.authorAllegrucci, C,en
dc.contributor.authorAlberio, R,en
dc.contributor.authorSurani, MA,en
dc.contributor.authorSurani, Azimen
dc.date.accessioned2017-08-01T11:14:52Z
dc.date.available2017-08-01T11:14:52Z
dc.date.issued2017-06-15en
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/265821
dc.description.abstractHuman primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during weeks 2–3 of early post-implantation development$^{1}$. Using $\textit{in vitro}$ models of hPGC induction$^{2, 3, 4}$, recent studies have suggested that there are marked mechanistic differences in the specification of human and mouse PGCs$^{5}$. This may be due in part to the divergence in their pluripotency networks and early post-implantation development$^{6, 7, 8}$. As early human embryos are not accessible for direct study, we considered alternatives including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs originate from the posterior pre-primitive-streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. We use this model together with human and monkey $\textit{in vitro}$ models simulating peri-gastrulation development to show the conserved principles of epiblast development for competency for primordial germ cell fate. This process is followed by initiation of the epigenetic program$^{9, 10, 11}$ and regulated by a balanced $\textit{SOX17–BLIMP1}$ gene dosage. Our combinatorial approach using human, porcine and monkey $\textit{in vivo}$ and $\textit{in vitro}$ models provides synthetic insights into early human development.
dc.description.sponsorshipWellcome Trust Medical Research Council BBSRC
dc.language.isoenen
dc.publisherNature Publishing Group
dc.titlePrinciples of early human development and germ cell program from observed model systemsen
dc.typeArticle
prism.endingPage420
prism.publicationDate2017en
prism.publicationNameNatureen
prism.startingPage416
prism.volume546en
dc.identifier.doi10.17863/CAM.10360
dcterms.dateAccepted2017-05-03en
rioxxterms.versionofrecord10.1038/nature22812en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-06-15en
dc.contributor.orcidSurani, Azim [0000-0002-8640-4318]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idUNIVERSITY OF NOTTINGHAM (FB BBSRC) (BB/M001466/1)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idMRC (MR/P009948/1)
pubs.funder-project-idWellcome Trust (096738/Z/11/Z)
cam.issuedOnline2017-06-07en
rioxxterms.freetoread.startdate2017-12-07


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