Vigano Maria Alessandra, Ivanek Robert, Balwierz Piotr, Berninger Philipp, van Nimwegen Erik, Karjalainen Klaus, Rolink Antonius
Developmental and Molecular Immunology Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
Eur J Immunol. 2014 Apr;44(4):1181-93. doi: 10.1002/eji.201344022. Epub 2014 Feb 1.
Cellular differentiation of the T-cell branch of the immune system begins with the HSC, which undergoes a series of stages characterized by progressive restriction in multipotency and acquisition of specific lineage identity At the molecular level, the restriction of cell potential, commitment, and differentiation to a specific lineage is achieved through the coordinated control of gene expression and epigenetic mechanisms. Here, we analyzed and compared the gene expression profiles and the genome-wide histone modification marks H3K4me3 (H3 lysine 4 trimethylation) and H3K27me3 (H3 lysine 27 trimethylation) in (i) in vitro propagated HSCs, (ii) in vitro generated and propagated pro-T cells derived from these stem cells, and (iii) double-positive thymocytes derived from these pro-T cells after injection into Rag-deficient mice. The combined analyses of the different datasets in this unique experimental system highlighted the importance of both transcriptional and epigenetic repression in shaping the early phases of T-cell development.
免疫系统T细胞分支的细胞分化始于造血干细胞（HSC），造血干细胞经历一系列阶段，其特征是多能性逐渐受限并获得特定谱系身份。在分子水平上，细胞潜能的限制、定向分化以及向特定谱系的分化是通过基因表达和表观遗传机制的协调控制来实现的。在这里，我们分析并比较了以下细胞中的基因表达谱以及全基因组组蛋白修饰标记H3K4me3（H3赖氨酸4三甲基化）和H3K27me3（H3赖氨酸27三甲基化）：（i）体外扩增的造血干细胞；（ii）从这些干细胞体外生成并扩增的前T细胞；（iii）将这些前T细胞注入Rag缺陷小鼠后产生的双阳性胸腺细胞。在这个独特的实验系统中对不同数据集的综合分析突出了转录抑制和表观遗传抑制在塑造T细胞发育早期阶段中的重要性。
