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Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development
dc.contributor.author | Landeira, David | |
dc.contributor.author | Bagci, Hakan | |
dc.contributor.author | Malinowski, Andrzej R. | |
dc.contributor.author | Brown, Karen E. | |
dc.contributor.author | Soza-Ried, Jorge | |
dc.contributor.author | Feytout, Amelie | |
dc.contributor.author | Webster, Zoe | |
dc.contributor.author | Ndjetehe, Elodie | |
dc.contributor.author | Cantone, Irene | |
dc.contributor.author | Asenjo, Helena G. | |
dc.contributor.author | Brockdorff, Neil | |
dc.contributor.author | Carroll, Thomas | |
dc.contributor.author | Merkenschlager, Matthias | |
dc.contributor.author | Fisher, Amanda G. | |
dc.date.accessioned | 2015-09-08T11:14:59Z | |
dc.date.available | 2015-09-08T11:14:59Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Landeira, D.; et al. Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development. Cell Reports, 12(4): 573-586 (2015). [http://hdl.handle.net/10481/37290] | es_ES |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/10481/37290 | |
dc.description.abstract | Jarid2 is part of the Polycomb Repressor complex 2 (PRC2) responsible for genome-wide H3K27me3 deposition. Unlike other PRC2-deficient embryonic stem cells (ESCs), however, Jarid2-deficient ESCs show a severe differentiation block, altered colony morphology, and distinctive patterns of deregulated gene expression. Here, we show that Jarid2−/− ESCs express constitutively high levels of Nanog but reduced PCP signaling components Wnt9a, Prickle1, and Fzd2 and lowered β-catenin activity. Depletion of Wnt9a/Prickle1/Fzd2 from wild-type ESCs or overexpression of Nanog largely phenocopies these cellular defects. Co-culture of Jarid2−/− with wild-type ESCs restores variable Nanog expression and β-catenin activity and can partially rescue the differentiation block of mutant cells. In addition, we show that ESCs lacking Jarid2 or Wnt9a/Prickle1/Fzd2 or overexpressing Nanog induce multiple ICM formation when injected into normal E3.5 blastocysts. These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development. | es_ES |
dc.description.sponsorship | This study was supported by the Medical Research Council, the ERC (H.B. and J.S.-R.) (#294627), the HFSP (I.C.), and the Spanish Ministry of Economy and Competitiveness (D.L. and H.G.A.) (RYC-2012-10019; SAF2013-40891-R). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | es_ES |
dc.subject | Cell self-renewal | es_ES |
dc.subject | Epiblast stem-cells | es_ES |
dc.subject | Beta-catenin | es_ES |
dc.subject | Gene expression | es_ES |
dc.subject | Polycom repression | es_ES |
dc.subject | Pluripotency | es_ES |
dc.title | Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.doi | 10.1016/j.celrep.2015.06.060 |