dc.contributor.author | Senft, AD | |
dc.contributor.author | Costello, I | |
dc.contributor.author | King, HW | |
dc.contributor.author | Mould, AW | |
dc.contributor.author | Bikoff, EK | |
dc.contributor.author | Robertson, EJ | |
dc.date.accessioned | 2019-03-01T08:57:42Z | |
dc.date.available | 2018-07-22 | |
dc.date.available | 2019-03-01T08:57:42Z | |
dc.date.issued | 2018-08-21 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/55623 | |
dc.description.abstract | Epiblast cells in the early post-implantation stage mammalian embryo undergo a transition described as lineage priming before cell fate allocation, but signaling pathways acting upstream remain ill defined. Genetic studies demonstrate that Smad2/3 double-mutant mouse embryos die shortly after implantation. To learn more about the molecular disturbances underlying this abrupt failure, here we characterized Smad2/3-deficient embryonic stem cells (ESCs). We found that Smad2/3 double-knockout ESCs induced to form epiblast-like cells (EpiLCs) display changes in naive and primed pluripotency marker gene expression, associated with the disruption of Oct4-bound distal regulatory elements. In the absence of Smad2/3, we observed enhanced Bmp target gene expression and de-repression of extra-embryonic gene expression. Cell fate allocation into all three embryonic germ layers is disrupted. Collectively, these experiments demonstrate that combinatorial Smad2/3 functional activities are required to maintain distinct embryonic and/or extra-embryonic cell identity during lineage priming in the epiblast before gastrulation.
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved. | en_US |
dc.format.extent | 1977-1985 | |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.ispartof | CELL REPORTS | |
dc.rights | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.title | Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2018 The Author(s). | |
dc.identifier.doi | 10.1016/j.celrep.2018.07.077 | |
pubs.author-url | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000442693600006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a | en_US |
pubs.issue | 8 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published | en_US |
pubs.publisher-url | https://doi.org/10.1016/j.celrep.2018.07.077 | |
pubs.volume | 24 | en_US |
dcterms.dateAccepted | 2018-07-22 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |