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Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling

Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is mostly unknown. Here we show that Eed deficiency in ch...

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Autores principales: Mirzamohammadi, Fatemeh, Papaioannou, Garyfallia, Inloes, Jennifer B., Rankin, Erinn B., Xie, Huafeng, Schipani, Ernestina, Orkin, Stuart H., Kobayashi, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917962/
https://www.ncbi.nlm.nih.gov/pubmed/27329220
http://dx.doi.org/10.1038/ncomms12047
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author Mirzamohammadi, Fatemeh
Papaioannou, Garyfallia
Inloes, Jennifer B.
Rankin, Erinn B.
Xie, Huafeng
Schipani, Ernestina
Orkin, Stuart H.
Kobayashi, Tatsuya
author_facet Mirzamohammadi, Fatemeh
Papaioannou, Garyfallia
Inloes, Jennifer B.
Rankin, Erinn B.
Xie, Huafeng
Schipani, Ernestina
Orkin, Stuart H.
Kobayashi, Tatsuya
author_sort Mirzamohammadi, Fatemeh
collection PubMed
description Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is mostly unknown. Here we show that Eed deficiency in chondrocytes causes severe kyphosis and a growth defect with decreased chondrocyte proliferation, accelerated hypertrophic differentiation and cell death with reduced Hif1a expression. Eed deficiency also causes induction of multiple signalling pathways in chondrocytes. Wnt signalling overactivation is responsible for the accelerated hypertrophic differentiation and kyphosis, whereas the overactivation of TGF-β signalling is responsible for the reduced proliferation and growth defect. Thus, our study demonstrates that PRC2 has an important regulatory role in lineage-committed tissue cells by suppressing overactivation of multiple signalling pathways.
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spelling pubmed-49179622016-07-07 Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling Mirzamohammadi, Fatemeh Papaioannou, Garyfallia Inloes, Jennifer B. Rankin, Erinn B. Xie, Huafeng Schipani, Ernestina Orkin, Stuart H. Kobayashi, Tatsuya Nat Commun Article Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is mostly unknown. Here we show that Eed deficiency in chondrocytes causes severe kyphosis and a growth defect with decreased chondrocyte proliferation, accelerated hypertrophic differentiation and cell death with reduced Hif1a expression. Eed deficiency also causes induction of multiple signalling pathways in chondrocytes. Wnt signalling overactivation is responsible for the accelerated hypertrophic differentiation and kyphosis, whereas the overactivation of TGF-β signalling is responsible for the reduced proliferation and growth defect. Thus, our study demonstrates that PRC2 has an important regulatory role in lineage-committed tissue cells by suppressing overactivation of multiple signalling pathways. Nature Publishing Group 2016-06-22 /pmc/articles/PMC4917962/ /pubmed/27329220 http://dx.doi.org/10.1038/ncomms12047 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Mirzamohammadi, Fatemeh
Papaioannou, Garyfallia
Inloes, Jennifer B.
Rankin, Erinn B.
Xie, Huafeng
Schipani, Ernestina
Orkin, Stuart H.
Kobayashi, Tatsuya
Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling
title Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling
title_full Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling
title_fullStr Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling
title_full_unstemmed Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling
title_short Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling
title_sort polycomb repressive complex 2 regulates skeletal growth by suppressing wnt and tgf-β signalling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917962/
https://www.ncbi.nlm.nih.gov/pubmed/27329220
http://dx.doi.org/10.1038/ncomms12047
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