An Essential Developmental Checkpoint for Production of the T Cell Lineage
An Essential Developmental Checkpoint for Production of the T Cell Lineage
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DOI：
10.1126/science.1188995
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发表时间：
2010-07-02
期刊：
影响因子：
56.9
通讯作者：
Kawamoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Ikawa, Tomokatsu;Hirose, Satoshi;Kawamoto, Hiroshi
在早期T细胞发育中，祖细胞保留产生髓系和自然杀伤细胞谱系的潜力，最终被确定为特定的T细胞谱系。驱动这一决定步骤的分子机制尚不清楚。我们发现，当小鼠造血祖细胞在固定的Notch配体DLL4蛋白上培养时，在包括白细胞介素-7在内的细胞因子混合物的存在下，向T细胞发展的祖细胞被阻止，被阻止的细胞进入自我更新周期，保持非T谱系的潜力。白细胞介素-7浓度降低促进T细胞谱系测定。在缺乏转录因子Bcl11b的小鼠胸腺细胞中也观察到类似的祖细胞阻滞和自我更新。因此，我们的研究确定了T细胞发育过程中最早的检查点，并表明它依赖于bcl11b。
In early T cell development, progenitors retaining the potential to generate myeloid and natural killer lineages are eventually determined to a specific T cell lineage. The molecular mechanisms that drive this determination step remain unclarified. We show that, when murine hematopoietic progenitors were cultured on immobilized Notch ligand DLL4 protein in the presence of a cocktail of cytokines including interleukin-7, progenitors developing toward T cells were arrested and the arrested cells entered a self-renewal cycle, maintaining non-T lineage potentials. Reduced concentrations of interleukin-7 promoted T cell lineage determination. A similar arrest and self-renewal of progenitors were observed in thymocytes of mice deficient in the transcription factor Bcl11b. Our study thus identifies the earliest checkpoint during T cell development and shows that it is Bcl11b-dependent.