Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
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.
Nat Commun. 2016 Jun 22;7:12047. doi: 10.1038/ncomms12047.
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.
多梳抑制复合物 2（PRC2）通过抑制调节细胞分化和组织发育的基因来控制干细胞的维持和谱系决定。然而，PRC2 在定向分化的体细胞中的作用大多未知。在这里，我们显示软骨细胞中 Eed 的缺乏导致严重的脊柱后凸和生长缺陷，伴随着软骨细胞增殖减少、肥大分化加速和细胞死亡，Hif1a 表达降低。Eed 缺乏还导致软骨细胞中多种信号通路的诱导。Wnt 信号过度激活是导致肥大分化和脊柱后凸的原因，而 TGF-β 信号过度激活是导致增殖减少和生长缺陷的原因。因此，我们的研究表明，PRC2 通过抑制多种信号通路的过度激活，在定向分化的组织细胞中发挥重要的调节作用。
