title: Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling.
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.
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mirzamohammadi
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
authors.forename: Garyfallia
authors.initials: G
authors.lastname: Papaioannou
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Inloes
authors.affiliation: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Center for Clinical Sciences Research, Stanford University, 875 Blake Wilbur Drive, Stanford, California, 94305, USA.
authors.forename: Erinn B
authors.initials: EB
authors.lastname: Rankin
authors.affiliation: Department of Pediatric Oncology, Children's Hospital, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Orthopaedic Surgery, Medical School, University of Michigan, Ann Arbor, 1500 E Medical Center Drive, Ann Arbor, Michigan 48109, USA.
authors.forename: Ernestina
authors.initials: E
authors.lastname: Schipani
authors.affiliation: Department of Pediatric Oncology, Children's Hospital, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology*; D005260:Female; D017353:Gene Deletion; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007738:Kyphosis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: C107275:Eed protein, mouse; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D063151:Polycomb Repressive Complex 2