Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782439031758389248 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4917962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mirzamohammadifatemeh polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling AT papaioannougaryfallia polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling AT inloesjenniferb polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling AT rankinerinnb polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling AT xiehuafeng polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling AT schipaniernestina polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling AT orkinstuarth polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling AT kobayashitatsuya polycombrepressivecomplex2regulatesskeletalgrowthbysuppressingwntandtgfbsignalling |