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

Fatemeh Mirzamohammadi, Garyfallia Papaioannou, Jennifer B. Inloes, Erinn B. Rankin, Huafeng Xie, Ernestina Schipani, Stuart H. Orkin and Tatsuya Kobayashi ()
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Fatemeh Mirzamohammadi: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School
Garyfallia Papaioannou: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School
Jennifer B. Inloes: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School
Erinn B. Rankin: Center for Clinical Sciences Research, Stanford University
Huafeng Xie: Children’s Hospital, Dana Farber Cancer Institute
Ernestina Schipani: Medical School, University of Michigan
Stuart H. Orkin: Children’s Hospital, Dana Farber Cancer Institute
Tatsuya Kobayashi: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms12047

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