Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-[beta] 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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Published inNature communications Vol. 7; p. 12047
Main Authors Mirzamohammadi, Fatemeh, Papaioannou, Garyfallia, Inloes, Jennifer B, Rankin, Erinn B, Xie, Huafeng, Schipani, Ernestina, Orkin, Stuart H, Kobayashi, Tatsuya
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 01.06.2016
Subjects
Apoptosis
Cartilage
Cell death
Chondrocytes
Chondrogenesis
Differentiation (biology)
Epigenetics
Eutrophication
Gene expression
Hypoxia
Kinases
Kyphosis
Polycomb group proteins
Proteins
Radiation
Signal transduction
Signaling
Somatic cells
Stem cells
Tissues
Wnt protein
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Summary: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.
ISSN:2041-1723
DOI:10.1038/ncomms12047