期刊
CELL REPORTS
卷 12, 期 4, 页码 573-586出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.06.060
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类别
资金
- Medical Research Council
- ERC [294627]
- HFSP
- Spanish Ministry of Economy and Competitiveness [RYC-2012-10019, SAF2013-40891-R]
- European Research Council (ERC) [294627] Funding Source: European Research Council (ERC)
- Medical Research Council [MC_U120027516] Funding Source: researchfish
- MRC [MC_U120027516] Funding Source: UKRI
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 beta-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 beta-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.
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