Requirement for Notch1 signals at sequential early stages of intrathymic T cell development
Requirement for Notch1 signals at sequential early stages of intrathymic T cell development
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DOI：
10.1038/ni1217
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发表时间：
2005-07-01
影响因子：
30.5
通讯作者：
Guidos, CJ
中科院分区：
文献类型：
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作者：
Tan, JB;Visan, I;Guidos, CJ
通过跨膜Notch1受体的信号传导指导胸腺播种祖细胞（TSP）抑制其B细胞潜能并“选择"T细胞命运。目前的范例表明，TSP包含在胸腺细胞的多能早期T谱系前体（ETP）子集。然而，我们在这里表明，ETP的B细胞的潜力并没有在限制Notch1激活的微环境中增强。此外，低阈值Notch1信号抑制B细胞生产的TSP之前，他们达到ETP阶段。需要更高阈值的Notch1信号来驱动ETP增殖并发育成CD4（+）CD8（+）双阳性胸腺细胞。因此，TSP可以通过其强大的B细胞潜能和对Notch 1信号的灵敏度与所有先前鉴定的早期T细胞祖细胞区分开。
Signaling through the transmembrane Notch1 receptor directs thymus-seeding progenitors (TSPs) to suppress their B cell potential and 'choose' the T cell fate. Present paradigms suggest that TSPs are contained in the multipotent early T lineage precursor (ETP) subset of thymocytes. However, we show here that the B cell potential of ETPs was not augmented in microenvironments that limited Notch1 activation. Furthermore, low-threshold Notch1 signals suppressed B cell production by TSPs before they reached the ETP stage. Notch1 signals of a higher threshold were needed to drive proliferation of ETPs and development into CD4(+)CD8(+) double-positive thymocytes. Thus, TSPs can be differentiated from all previously identified early T cell progenitors by their robust B cell potential and exquisite sensitivity to Notch1 signals.