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Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development

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Title: Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development
Authors: Landeira, D
Bagci, H
Malinowski, AR
Brown, KE
Soza-Ried, J
Feytout, A
Webster, Z
Ndjetehe, E
Cantone, I
Asenjo, HG
Brockdorff, N
Carroll, T
Merkenschlager, M
Fisher, AG
Item Type: Journal Article
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.
Issue Date: 16-Jul-2015
Date of Acceptance: 22-Jun-2015
URI: http://hdl.handle.net/10044/1/40190
DOI: http://dx.doi.org/10.1016/j.celrep.2015.06.060
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 573
End Page: 586
Journal / Book Title: Cell Reports
Volume: 12
Issue: 4
Copyright Statement: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 294627
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
CELL SELF-RENEWAL
EPIBLAST STEM-CELLS
BETA-CATENIN
GENE-EXPRESSION
POLYCOMB REPRESSION
WNT/BETA-CATENIN
MOUSE
PRC2
JUMONJI
PLURIPOTENCY
Adaptor Proteins, Signal Transducing
Animals
Blastocyst
Cell Differentiation
Cells, Cultured
Embryonic Stem Cells
Frizzled Receptors
Gene Expression Regulation, Developmental
Homeodomain Proteins
LIM Domain Proteins
Mice
Polycomb Repressive Complex 2
Wnt Proteins
Wnt Signaling Pathway
beta Catenin
Cells, Cultured
Blastocyst
Animals
Mice
Adaptor Proteins, Signal Transducing
Homeodomain Proteins
Cell Differentiation
Gene Expression Regulation, Developmental
Wnt Proteins
Frizzled Receptors
beta Catenin
Embryonic Stem Cells
LIM Domain Proteins
Wnt Signaling Pathway
Polycomb Repressive Complex 2
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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