Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells
Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells
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DOI：
10.1038/ni.2641
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发表时间：
2013-08-01
影响因子：
30.5
通讯作者：
Grosschedl, Rudolf
中科院分区：
文献类型：
--
作者：
Nechanitzky, Robert;Akbas, Duygu;Grosschedl, Rudolf
转录因子EBF1和Pax5分别与B细胞谱系程序的激活和替代谱系潜能的不可逆丧失（承诺）有关。在这里，我们有条件地删除转移到淋巴小鼠的前b细胞中的Ebf1。我们发现这些细胞转化为先天淋巴样细胞（ILCs）和T细胞，其编码B细胞和T细胞抗原受体的位点具有可变多样性连接（VDJ）重排。作为谱系转换的中间产物，可以检测到表达Pax5和ILC和T细胞命运转录调节因子的ebf1缺陷CD19（+）细胞。特别是，编码转录因子Id2和TCF-1的基因被EBF1结合并抑制。因此，EBF1和Pax5都是通过抑制不同的和共同的细胞命运决定因素来实现B谱系承诺所必需的。
The transcription factors EBF1 and Pax5 have been linked to activation of the B cell lineage program and irreversible loss of alternative lineage potential (commitment), respectively. Here we conditionally deleted Ebf1 in committed pro-B cells after transfer into alymphoid mice. We found that those cells converted into innate lymphoid cells (ILCs) and T cells with variable-diversity- joining (VDJ) rearrangements of loci encoding both B cell and T cell antigen receptors. As intermediates in lineage conversion, Ebf1-deficient CD19(+) cells expressing Pax5 and transcriptional regulators of the ILC and T cell fates were detectable. In particular, genes encoding the transcription factors Id2 and TCF-1 were bound and repressed by EBF1. Thus, both EBF1 and Pax5 are required for B lineage commitment by repressing distinct and common determinants of alternative cell fates.