HEBAlt enhances the T-cell potential of fetal myeloid-biased precursors
HEBAlt enhances the T-cell potential of fetal myeloid-biased precursors
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DOI：
10.1093/intimm/dxq450
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发表时间：
2010-12-01
影响因子：
4.4
通讯作者：
Anderson, Michele K.
中科院分区：
文献类型：
--
作者：
Braunstein, Marsela;Rajkumar, Paula;Anderson, Michele K.
造血受转录因子和环境信号之间的相互作用控制。T谱系选择的主要决定因素之一是Delta样（DL）-Notch信号传导，其促进T细胞发育并抑制B细胞发育。我们已经发现，转录因子HEBAlt在早期造血前体中响应于DL-Notch信号传导而上调，并且它可以促进早期T细胞发育。在此，我们在小鼠胎肝中鉴定了一群谱系阴性的Sca-1（-）c-kit（+）（LK）细胞，它们迅速产生髓样细胞和B细胞，但表现出非常少的T细胞潜能。然而，HEBAlt在这些前体中的强制表达恢复了它们发育成T细胞的能力。我们还表明，Ikaros和Notch 1响应于HEBAlt过表达而上调，并且活化的Notch 1增强LK细胞进入T细胞谱系的能力。此外，髓系转录因子C/EBP α响应于HEBAlt而下调。因此，我们认为HEBAlt在造血过程中执行T-谱系命运并限制骨髓命运的网络中发挥作用。
Hematopoiesis is controlled by the interplay between transcription factors and environmental signals. One of the primary determinants of the T-lineage choice is Delta-like (DL)-Notch signaling, which promotes T-cell development and inhibits B-cell development. We have found that the transcription factor HEBAlt is up-regulated in early hematopoietic precursors in response to DL-Notch signaling and that it can promote early T-cell development. Here, we identified a population of lineage-negative Sca-1(-)c-kit(+) (LK) cells in the mouse fetal liver that rapidly gave rise to myeloid cells and B cells but exhibited very little T-cell potential. However, forced expression of HEBAlt in these precursors restored their ability to develop into T cells. We also showed that Ikaros and Notch1 are up-regulated in response to HEBAlt over-expression and that activated Notch1 enhances the ability of LK cells to enter the T-cell lineage. Furthermore, the myeloid transcription factor C/EBP alpha is down-regulated in response to HEBAlt. We therefore propose that HEBAlt plays a role in the network that enforces the T-lineage fate and limits myeloid fate during hematopoiesis.