Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones
Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones
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DOI：
10.1016/j.bone.2018.10.021
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发表时间：
2019-03-01
期刊：
影响因子：
4.1
通讯作者：
Fukami, Maki
中科院分区：
文献类型：
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作者：
Katoh-Fukui, Yuko;Baba, Takashi;Fukami, Maki
一组关键的发育基因对断奶时多能祖细胞的骨骼生长至关重要。调节这些基因的多梳组蛋白通过表观遗传染色质修饰和重塑有助于细胞谱系定型和随后的分化。然而，目前还不清楚在骨骼生长过程中，多梳蛋白靶向哪些细胞谱系和基因集。我们现在报告，小鼠缺乏polycomb组基因cbx 2（cterm/cterm）表现出骨骼发育不全的胫骨，股骨和颅骨。这些小鼠的长骨腔中含有较少的多能间充质基质细胞。骨髓细胞的RNA测序分别显示成骨细胞和脂肪形成基因的下调和上调。此外，在B细胞前体中特异性表达的基因的表达水平降低。在cbx 2（cterm/cterm）骨髓基质细胞中强制表达Cbx 2恢复成纤维细胞集落形成并抑制成脂分化。总的来说，我们的研究结果表明，Cbx 2控制骨髓间充质基质细胞的维持和成脂分化。
A set of key developmental genes is essential for skeletal growth from multipotent progenitor cells at weaning. Polycomb group proteins, which regulate such genes contributes to the cell lineage commitment and subsequent differentiation via epigenetic chromatin modification and remodeling. However, it is unclear which cell lineage and gene sets are targeted by polycomb proteins during skeletal growth. We now report that mice deficient in a polycomb group gene cbx2(cterm/cterm) exhibited skeletal hypoplasia in the tibia, femur, and cranium. Long bone cavities in these mice contained fewer multipotent mesenchymal stromal cells. RNA-sequencing of bone marrow cells showed downregulation and upregulation of osteoblastic and adipogenic genes, respectively. Furthermore, the expression levels of genes specifically expressed in B-cell precursors were decreased. Forced expression of Cbx2 in cbx2(cterm/cterm) bone marrow stromal cell recovered fibroblastic colony formation and suppressed adipogenic differentiation. Collectively, our results suggest that Cbx2 controls the maintenance and adipogenic differentiation of mesenchymal stromal cells in the bone marrow.