Determining c-Myb protein levels can isolate functional hematopoietic stem cell subtypes.
Determining c-Myb protein levels can isolate functional hematopoietic stem cell subtypes.
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测定 c-Myb 蛋白水平可以分离功能性造血干细胞亚型。
DOI：
10.1002/stem.1855
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Sakamoto H
中科院分区：
文献类型：
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作者：
Sakamoto H
转录因子c-Myb最初被鉴定为一种由两种禽白血病病毒编码的转化癌蛋白。随后，通过建立影响其表达的小鼠模型，c-Myb已被证明是造血的关键调节因子，包括在造血干细胞(HSCs)中发挥关键作用。C-Myb在造血干细胞中的确切功能尚不清楚。我们已经在小鼠身上产生了一种新的肌球，可以直接观察单细胞中c-Myb蛋白的水平。利用这一报道线，我们证明了可以根据它们各自的c-Myb蛋白表达水平来分离HSCs的亚型。低水平表达c-Myb蛋白的HSC(c-MyblowHSC)似乎代表了最不成熟、最休眠的HSC，它们是保留溴脱氧尿苷标记的HSC的主要组成部分。5-氟尿嘧啶诱导的造血应激反应表明，在这种情况下，表达c-Myb的细胞成为多系再繁殖的关键。基于c-Myb蛋白水平的HSC亚群的区别并不反映在c-mybmRNA的水平上，c-Myblows和c-MybHighHSC之间的差异不超过1.3倍。这表明，当旨在了解控制干细胞行为的调控网络时，包括蛋白质研究是多么重要。StemCells2015；33：479-490
The transcription factor c-Myb was originally identified as a transforming oncoprotein encoded by two avian leukemia viruses. Subsequently, through the generation of mouse models that affect its expression, c-Myb has been shown to be a key regulator of hematopoiesis, including having critical roles in hematopoietic stem cells (HSCs). The precise function of c-Myb in HSCs although remains unclear. We have generated a novelc-myballele in mice that allows direct observation of c-Myb protein levels in single cells. Using this reporter line we demonstrate that subtypes of HSCs can be isolated based upon their respective c-Myb protein expression levels. HSCs expressing low levels of c-Myb protein (c-MyblowHSC) appear to represent the most immature, dormant HSCs and they are a predominant component of HSCs that retain bromodeoxyuridine labeling. Hematopoietic stress, induced by 5-fluorouracil ablation, revealed that in this circumstance c-Myb-expressing cells become critical for multilineage repopulation. The discrimination of HSC subpopulations based on c-Myb protein levels is not reflected in the levels ofc-mybmRNA, there being no more than a 1.3-fold difference comparing c-Myblowand c-MybhighHSCs. This illustrates how essential it is to include protein studies when aiming to understand the regulatory networks that control stem cell behavior. StemCells2015;33:479–490