Harman Benjamin C, Jenkinson William E, Parnell Sonia M, Rossi Simona W, Jenkinson Eric J, Anderson Graham
Dept of Anatomy, Institute for Biomedical Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
Blood. 2005 Aug 1;106(3):886-92. doi: 10.1182/blood-2004-12-4881. Epub 2005 Apr 21.
Commitment of hemopoietic progenitors to the T-cell lineage is a crucial requirement for T-cell development, yet the timing and developmental cues regulating this process remain controversial. Here we have devised a technique to analyze the T-cell/B-cell lineage potential of precursors that have been recruited to the fetal mouse thymus but which have yet to contact the thymic epithelial microenvironment. We show that lymphoid progenitors arriving at the thymus are not bipotent T/B precursors, and provide evidence that intrathymic Notch signaling is not the mechanism determining T/B lineage choice in migrant precursors. Rather, we provide evidence that Notch signaling influences T/B lineage choice in lymphoid precursors through interactions with defined stromal components within the fetal liver. Collectively, our data redefine our understanding of the role and timing of Notch signaling in relation to lineage choices in lymphoid precursors.
造血祖细胞向T细胞谱系的定向分化是T细胞发育的关键要求，但调节这一过程的时间和发育线索仍存在争议。在这里，我们设计了一种技术，用于分析已被招募到胎鼠胸腺但尚未接触胸腺上皮微环境的前体细胞的T细胞/B细胞谱系潜能。我们发现，到达胸腺的淋巴祖细胞不是双能T/B前体细胞，并提供证据表明胸腺内Notch信号传导不是决定迁移前体细胞中T/B谱系选择的机制。相反，我们提供证据表明，Notch信号通过与胎肝内特定的基质成分相互作用，影响淋巴祖细胞中的T/B谱系选择。总的来说，我们的数据重新定义了我们对Notch信号在淋巴祖细胞谱系选择中的作用和时间的理解。
