Cbx4 regulates the proliferation of thymic epithelial cells and thymus function
Cbx4 regulates the proliferation of thymic epithelial cells and thymus function
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Cbx4调节胸腺上皮细胞增殖和胸腺功能
DOI：
10.1242/dev.085035
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发表时间：
2013-02-15
期刊：
影响因子：
4.6
通讯作者：
Xu, Guo-Liang
中科院分区：
文献类型：
--
作者：
Liu, Bo;Liu, Yuan-Feng;Xu, Guo-Liang
胸腺上皮细胞(TECs)是胸腺基质的主要成分，支持T细胞的增殖和谱系选择。在这里，我们证明了Cbx4，一种在胸腺上皮细胞中高度表达的多梳蛋白，在胸腺器官发生中具有必要的和非多余的作用。靶向阻断Cbx4会导致胎儿胸腺严重发育不良，这是胸腺细胞增殖减少的结果。Cbx4的细胞特异性缺失表明，受损的胸腺生成植根于有缺陷的上皮室。Cbx4基因缺陷的TECs表现出增殖能力受损，在出生后突变的小鼠中，有限的胸腺上皮结构迅速恶化，导致出生后不久T细胞发育几乎完全受阻，成年小鼠外周T细胞数量显著减少。此外，我们还证明了Cbx4与p63在物理上相互作用并在功能上相关，p63是一种转录调节因子，被认为对维持上皮祖细胞的干性很重要。总之，这些数据证明Cbx4是胸腺上皮生成和维持的关键调节因子，因此也是胸腺细胞发育的关键调节因子。
Thymic epithelial cells (TECs) are the main component of the thymic stroma, which supports T-cell proliferation and repertoire selection. Here, we demonstrate that Cbx4, a Polycomb protein that is highly expressed in the thymic epithelium, has an essential and non-redundant role in thymic organogenesis. Targeted disruption of Cbx4 causes severe hypoplasia of the fetal thymus as a result of reduced thymocyte proliferation. Cell-specific deletion of Cbx4 shows that the compromised thymopoiesis is rooted in a defective epithelial compartment. Cbx4-deficient TECs exhibit impaired proliferative capacity, and the limited thymic epithelial architecture quickly deteriorates in postnatal mutant mice, leading to an almost complete blockade of T-cell development shortly after birth and markedly reduced peripheral T-cell populations in adult mice. Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of epithelial progenitors. Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development.