Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the notch pathway
Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the notch pathway
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DOI：
10.4049/jimmunol.174.5.2507
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Kanno, M
中科院分区：
文献类型：
--
作者：
Miyazaki, M;Kawamoto, H;Kanno, M
Polycomb group （PcG）蛋白通过调控基因表达，在多轮细胞分裂过程中维持细胞身份。在本报告中，我们证明了PcG基因mel-18的缺失会在TCR β链基因重排之前的一个阶段损害大多数未成熟T祖细胞在体内和体外的扩增。这些T祖细胞的损伤似乎与细胞死亡易感性增加有关。我们还发现，从mel-18（-/-）小鼠分离的早期T祖细胞中，Notch信号通路靶基因之一Hes-1的表达急剧下调。此外，mel-18(-/-) T前体在单层培养中不能维持Delta-like-1诱导的Hes-1表达。总的来说，这些数据表明mel-18有助于维持Hes-1基因作为细胞记忆系统的活性状态，从而支持早期T祖细胞的扩展。
Polycomb group (PcG) proteins play a role in the maintenance of cellular identity throughout many rounds of cell division through the regulation of gene expression. In this report we demonstrate that the loss of the PcG gene mel-18 impairs the expansion of the most immature T progenitor cells at a stage before the rearrangement of the TCR beta-chain gene in vivo and in vitro. This impairment of these T progenitors appears to be associated with increased susceptibility to cell death. We also show that the expression of Hes-1, one of the target genes of the Notch signaling pathway, is drastically down-regulated in early T progenitors isolated from mel-18(-/-) mice. In addition, mel-18(-/-) T precursors could not maintain the Hes-1 expression induced by Delta-like-1 in monolayer culture. Collectively, these data indicate that mel-18 contributes to the maintenance of the active state of the Hes-1 gene as a cellular memory system, thereby supporting the expansion of early T progenitors.