In vivo mapping of notch pathway activity in normal and stress hematopoiesis.

In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
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DOI:
10.1016/j.stem.2013.05.015
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发表时间:
2013-08-01
期刊:
影响因子:
23.9
通讯作者:
Aifantis, Iannis
Aifantis, Iannis
中科院分区:
医学1区
文献类型:
--
作者:
Oh, Philmo;Lobry, Camille;Gao, Jie;Tikhonova, Anastasia;Loizou, Evangelia;Manent, Jan;van Handel, Ben;Ibrahim, Sherif;Greve, Jeffrey;Mikkola, Hanna;Artavanis-Tsakonas, Spyros;Aifantis, Iannis

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越来越多的证据表明,Notch信号在造血过程中的多个点都很活跃。直到最近,大多数这样的研究集中在淋巴细胞分化中的Notch信号传导上,并且由于缺乏可用的遗传工具,对单个Notch受体作用的了解有限。在这份手稿中,我们生成并描述了动物模型,以识别和命运映射表达每种Notch受体的干细胞和祖细胞,描绘Notch通路激活,并进行体内功能获得和丧失研究,剖析早期造血中的Notch信号传导。这些模型提供了造血干细胞和祖细胞中谱系特异性Notch受体表达和活化的全面遗传图谱。此外,他们建立了Notch信号传导在血液祖细胞向红细胞谱系的定型中的先前未知的作用,并将Notch信号传导与对应激红细胞生成的最佳生物反应联系起来。
Accumulating evidence suggests that Notch signaling is active at multiple points during hematopoiesis. Until recently, the majority of such studies focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles has been limited due to a paucity of genetic tools available. In this manuscript we generate and describe animal models to identify and fate-map stem and progenitor cells expressing each Notch receptor, delineate Notch pathway activation, and perform in vivo gain and loss of function studies dissecting Notch signaling in early hematopoiesis. These models provide comprehensive genetic maps of lineage-specific Notch receptor expression and activation in hematopoietic stem and progenitor cells. Moreover, they establish a previously unknown role for Notch signaling in the commitment of blood progenitors towards the erythrocytic lineage and link Notch signaling to optimal organismal response to stress erythropoiesis.
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