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首页> 外文期刊>Nature immunology >Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation.
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Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation.

机译:在B细胞分化的各个阶段,转录因子Foxo1具有不同的功能。

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摘要

The transcription factors Foxo1, Foxo3 and Foxo4 modulate cell fate 'decisions' in diverse systems. Here we show that Foxo1-dependent gene expression was critical at many stages of B cell differentiation. Early deletion of Foxo1 caused a substantial block at the pro-B cell stage due to a failure to express interleukin 7 receptor-alpha. Foxo1 inactivation in late pro-B cells resulted in an arrest at the pre-B cell stage due to lower expression of the recombination-activating genes Rag1 and Rag2. Deletion of Foxo1 in peripheral B cells led to fewer lymph node B cells due to lower expression of L-selectin and failed class-switch recombination due to impaired upregulation of the gene encoding activation-induced cytidine deaminase. Thus, Foxo1 regulates a transcriptional program that is essential for early B cell development and peripheral B cell function.
机译:转录因子Foxo1,Foxo3和Foxo4在不同系统中调节细胞命运的“决定”。在这里,我们显示Foxo1依赖基因表达在B细胞分化的许多阶段至关重要。 Foxo1的早期缺失由于无法表达白介素7受体-α而在pro-B细胞阶段造成了实质性的阻滞。由于重组激活基因Rag1和Rag2的较低表达,晚期pro-B细胞中的Foxo1失活导致其在pre-B细胞阶段停滞。由于L-选择蛋白的表达降低,外周B细胞Foxo1的缺失导致淋巴结B细胞减少,并且由于激活激活的胞苷脱氨酶编码基因的上调受损,导致类开关重组失败。因此,Foxo1调节转录程序,这对于早期B细胞发育和外周B细胞功能至关重要。

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