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

Nat Commun. 2016 Jun 22:7:12047. doi: 10.1038/ncomms12047.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bone and Bones / metabolism*
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Chondrocytes / cytology*
  • Female
  • Gene Deletion
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Kyphosis
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Signal Transduction
  • Stem Cells / cytology
  • Transforming Growth Factor beta / metabolism*
  • Wnt Proteins / metabolism*

Substances

  • Eed protein, mouse
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Polycomb Repressive Complex 2