Immature CD8 Single-Positive Thymocytes Are a Molecularly Distinct Subpopulation, Selectively Dependent on BRD4 for Their Differentiation

被引:21
作者
Gegonne, Anne [1 ]
Chen, Qing-Rong [2 ]
Dey, Anup [3 ]
Etzensperger, Ruth [1 ]
Tai, Xuguang [1 ]
Singer, Alfred [1 ]
Meerzaman, Daoud [2 ]
Ozato, Keiko [3 ]
Singer, Dinah S. [1 ]
机构
[1] NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA
[2] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD 20892 USA
[3] NICHHD, Div Dev Biol, NIH, Bethesda, MD 20892 USA
关键词
BROMODOMAIN PROTEIN; EXPRESSION; TRANSCRIPTION; PROLIFERATION; REPLICATION; RECOGNITION; PROGRESSION; MICE;
D O I
10.1016/j.celrep.2018.06.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:117 / 129
页数:13
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