Merkenschlager Matthias, Amoils Shannon, Roldan Esther, Rahemtulla Amin, O'connor Eric, Fisher Amanda G, Brown Karen E
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
J Exp Med. 2004 Dec 6;200(11):1437-44. doi: 10.1084/jem.20041127.
The differentiation of CD4(+) CD8(+) double positive (DP) thymocytes requires the irreversible choice between two alternative lineages, distinguished by the mutually exclusive expression of either CD4 or CD8. Differentiating DP cells transiently down-regulate both CD4 and CD8, and this has complicated the debate whether the mechanism of CD4/CD8 lineage choice is instructive, stochastic/selective, or more complex in nature. Using fluorescence in situ hybridization, we show that the stable silencing of coreceptor loci, and ultimately lineage choice, is predicted by the spatial repositioning of coreceptor alleles to centromeric heterochromatin domains. These data provide evidence that lineage-specific developmental programs are established early during the transition from the DP to the single positive stage.
CD4(+)CD8(+)双阳性（DP）胸腺细胞的分化需要在两个替代谱系之间做出不可逆的选择，这两个谱系通过CD4或CD8的相互排斥表达来区分。正在分化的DP细胞会短暂下调CD4和CD8，这使得关于CD4/CD8谱系选择机制是指导性的、随机/选择性的还是本质上更复杂的争论变得复杂。使用荧光原位杂交技术，我们表明共受体基因座的稳定沉默以及最终的谱系选择可通过共受体等位基因向着丝粒异染色质结构域的空间重新定位来预测。这些数据提供了证据，表明谱系特异性发育程序在从DP阶段向单阳性阶段转变的早期就已建立。
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