Koch U, Lacombe T A, Holland D, Bowman J L, Cohen B L, Egan S E, Guidos C J
Program in Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Canada.
Immunity. 2001 Aug;15(2):225-36. doi: 10.1016/s1074-7613(01)00189-3.
Notch-1 signaling is essential for lymphoid progenitors to undergo T cell commitment, but the mechanism has not been defined. Here we show that thymocytes ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling, induce lymphoid progenitors to develop into B cells in the thymus. This cell fate switch resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed by experiments utilizing lymphoid progenitors in which Notch-1 activity was genetically manipulated. These data identify Lunatic Fringe as a potent regulator of Notch-1 during the T/B lineage decision and show that an important function of Notch-1 in T cell commitment is to suppress B cell development in the thymus.
Notch-1信号对于淋巴祖细胞进行T细胞定向分化至关重要，但其机制尚未明确。在此我们表明，异位表达Notch-1信号修饰因子Lunatic Fringe的胸腺细胞可诱导淋巴祖细胞在胸腺中发育为B细胞。如利用对Notch-1活性进行基因操作的淋巴祖细胞所做实验所示，这种细胞命运转变是由Lunatic Fringe介导的对Notch-1功能的抑制所致。这些数据确定Lunatic Fringe是T/B谱系决定过程中Notch-1的有效调节因子，并表明Notch-1在T细胞定向分化中的一个重要功能是抑制胸腺中B细胞的发育。
