Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Rockville, MD 20892, USA.
Cell Rep. 2018 Jul 3;24(1):117-129. doi: 10.1016/j.celrep.2018.06.007.
T cell differentiation in the thymus proceeds in an ordered sequence of developmental events characterized by variable expression of CD4 and CD8 coreceptors. Here, we report that immature single-positive (ISP) thymocytes are molecularly distinct from all other T cell populations in the thymus in their expression of a gene profile that is dependent on the transcription factor BRD4. Conditional deletion of BRD4 at various stages of thymic differentiation reveals that BRD4 selectively regulates the further differentiation of ISPs by targeting cell cycle and metabolic pathways, but it does not affect the extensive proliferation that results in the generation of ISPs. These studies lead to the conclusion that the ISP subpopulation is not a hybrid transitional state but a molecularly distinct subpopulation that is selectively dependent on BRD4.
T 细胞在胸腺中的分化是一个有序的发育事件序列，其特征是 CD4 和 CD8 核心受体的可变表达。在这里，我们报告说，未成熟的单阳性（ISP）胸腺细胞在其基因表达谱上与胸腺中的所有其他 T 细胞群体明显不同，该基因表达谱依赖于转录因子 BRD4。在胸腺分化的各个阶段条件性删除 BRD4 表明，BRD4 通过靶向细胞周期和代谢途径选择性地调节 ISP 的进一步分化，但不影响导致 ISP 产生的广泛增殖。这些研究得出的结论是，ISP 亚群不是一种混合过渡状态，而是一种在分子上明显不同的亚群，它选择性地依赖于 BRD4。
