Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5
Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5
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DOI：
10.1038/ni1555
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发表时间：
2008-02-01
影响因子：
30.5
通讯作者：
Singh, Harinder
中科院分区：
文献类型：
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作者：
Pongubala, Jagan M. R.;Northrup, Daniel L.;Singh, Harinder
替代性谱系限制和B细胞Fl命运决定需要转录因子Pax5，但早期B细胞因子（EBF）在这些过程中的功能在很大程度上仍未被探索。在此我们表明，在缺乏EBF的情况下，“可扩增的”和克隆性淋巴祖细胞保留了相当大的髓系潜能。相反，在多能祖细胞中异位表达EBF会以牺牲髓系细胞命运为代价引导B细胞生成。EBF诱导Pax5并拮抗编码转录因子C/EBPα、PU.1和Id2的基因的表达。值得注意的是，在Pax5 -/-造血祖细胞中持续表达EBF足以在体内阻断它们的髓系和T谱系潜能。此外，在Pax5 -/-原B细胞中，较高的EBF表达抑制了替代性谱系基因。因此，EBF能够限制替代性谱系“选择”并独立于Pax5促进向B细胞命运的决定。
Alternative lineage restriction and B cel Fl fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates. EBF induced Pax5 and antagonized expression of genes encoding the transcription factors C/EBP alpha, PU.1 and Id2. Notably, sustained expression of EBF in Pax5(-/-) hematopoietic progenitor cells was sufficient to block their myeloid and T lineage potential in vivo. Furthermore, in Pax5(-/-) pro-B cells, higher EBF expression repressed alternative lineage genes. Thus, EBF can restrict alternative lineage 'choice' and promote commitment to the B cell fate independently of Pax5.