Imperial College London

ProfessorMatthiasMerkenschlager

Faculty of MedicineInstitute of Clinical Sciences

Professor of Cell Biology
 
 
 
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Contact

 

+44 (0)20 3313 8239matthias.merkenschlager

 
 
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Location

 

5.11DLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Landeira:2015:10.1016/j.celrep.2015.06.060,
author = {Landeira, D and Bagci, H and Malinowski, AR and Brown, KE and Soza-Ried, J and Feytout, A and Webster, Z and Ndjetehe, E and Cantone, I and Asenjo, HG and Brockdorff, N and Carroll, T and Merkenschlager, M and Fisher, AG},
doi = {10.1016/j.celrep.2015.06.060},
journal = {Cell Reports},
pages = {573--586},
title = {Jarid2 coordinates nanog expression and PCP/Wnt signaling required for efficient ESC differentiation and early embryo development},
url = {http://dx.doi.org/10.1016/j.celrep.2015.06.060},
volume = {12},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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.
AU - Landeira,D
AU - Bagci,H
AU - Malinowski,AR
AU - Brown,KE
AU - Soza-Ried,J
AU - Feytout,A
AU - Webster,Z
AU - Ndjetehe,E
AU - Cantone,I
AU - Asenjo,HG
AU - Brockdorff,N
AU - Carroll,T
AU - Merkenschlager,M
AU - Fisher,AG
DO - 10.1016/j.celrep.2015.06.060
EP - 586
PY - 2015///
SN - 2211-1247
SP - 573
TI - Jarid2 coordinates nanog expression and PCP/Wnt signaling required for efficient ESC differentiation and early embryo development
T2 - Cell Reports
UR - http://dx.doi.org/10.1016/j.celrep.2015.06.060
UR - https://www.sciencedirect.com/science/article/pii/S2211124715006865?via%3Dihub
UR - http://hdl.handle.net/10044/1/40190
VL - 12
ER -