@misc{10481/37290,
year = {2015},
url = {http://hdl.handle.net/10481/37290},
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.},
organization = {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).},
publisher = {Elsevier},
keywords = {Cell self-renewal},
keywords = {Epiblast stem-cells},
keywords = {Beta-catenin},
keywords = {Gene expression},
keywords = {Polycom repression},
keywords = {Pluripotency},
title = {Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development},
doi = {10.1016/j.celrep.2015.06.060},
author = {Landeira, David and Bagci, Hakan and Malinowski, Andrzej R. and Brown, Karen E. and Soza-Ried, Jorge and Feytout, Amelie and Webster, Zoe and Ndjetehe, Elodie and Cantone, Irene and Asenjo, Helena G. and Brockdorff, Neil and Carroll, Thomas and Merkenschlager, Matthias and Fisher, Amanda G.},
}