Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development Landeira, David Bagci, Hakan Malinowski, Andrzej R. Brown, Karen E. Soza-Ried, Jorge Feytout, Amelie Webster, Zoe Ndjetehe, Elodie Cantone, Irene Asenjo, Helena G. Brockdorff, Neil Carroll, Thomas Merkenschlager, Matthias Fisher, Amanda G. Cell self-renewal Epiblast stem-cells Beta-catenin Gene expression Polycom repression Pluripotency 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. 2015-09-08T11:14:59Z 2015-09-08T11:14:59Z 2015 journal article 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] 2211-1247 http://hdl.handle.net/10481/37290 10.1016/j.celrep.2015.06.060 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Elsevier