Clock gene Bmal1 is dispensable for intrinsic properties of murine hematopoietic stem cells.
Clock gene Bmal1 is dispensable for intrinsic properties of murine hematopoietic stem cells.
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DOI：
10.1186/1477-5751-13-4
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发表时间：
2014-03-08
期刊：
影响因子：
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通讯作者：
Yamazaki S
中科院分区：
文献类型：
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作者：
Ieyasu A;Tajima Y;Shimba S;Nakauchi H;Yamazaki S
昼夜节律影响着细胞周期、睡眠-觉醒节律、激素释放和其他重要的生理功能等多种生物现象。鉴于冬眠造血干细胞（HSC）的细胞周期进入在控制造血中起着关键作用，我们询问了时钟基因Bmal 1的功能意义，该基因作为转录因子在调节昼夜节律中起着核心作用。在这里，我们调查的必要性Bmal 1 HSC功能使用Bmal 1缺陷（Bmal 1-/-）小鼠。使用体外集落形成试验，我们发现Bmal 1 +/+和Bmal 1 −/− CD 34 −KSL细胞之间的混合集落形成频率没有显著差异。竞争性骨髓分析还显示，Bmal 1 −/−骨髓细胞与野生型细胞正常竞争，并显示出长期的多造血谱系重建。此外，Bmal 1 +/+和Bmal 1 −/−小鼠之间骨髓HSC的频率和冬眠状态没有显著差异，表明它们不依赖于昼夜节律。本文讨论了HSC功能的昼夜节律的必要性。我们的数据清楚地表明，一个关键的生物钟基因Bmal 1是决定HSC的内在功能，如分化，增殖和再生能力。
Circadian rhythms are known to influence a variety of biological phenomena such as cell cycle, sleep-wake rhythm, hormone release and other important physiological functions. Given that cell cycle entry of hibernating hematopoietic stem cells (HSCs) plays a critical role in controlling hematopoiesis, we asked functional significance of the clock gene Bmal1, which plays a central role in regulating circadian rhythms as a transcription factor. Here we investigated the necessity of Bmal1 for HSC functions using Bmal1 deficient (Bmal1−/−) mice. Using colony-forming assays in vitro, we found that the frequency of mixed colony formation between Bmal1+/+ and Bmal1−/− CD34−KSL cells does not differ significantly. Competitive bone marrow assays also revealed that Bmal1−/− bone marrow cells competed normally with wild-type cells and displayed long-term multi-hematopoietic lineage reconstitution. In addition, there were no significant differences in the frequencies and hibernation state of bone marrow HSCs between Bmal1+/+ and Bmal1−/− mice, suggesting that they are independent of circadian rhythms. This paper discusses the necessity of circadian rhythms for HSC functions. Our data clearly shows that a key circadian clock gene Bmal1 is dispensable for intrinsic functions of HSCs, such as differentiation, proliferation and repopulating ability.