NF-Y is necessary for hematopoietic stem cell proliferation and survival
NF-Y is necessary for hematopoietic stem cell proliferation and survival
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DOI：
10.1182/blood-2011-06-359406
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发表时间：
2012-02-09
期刊：
影响因子：
20.3
通讯作者：
Emerson, Stephen G.
中科院分区：
文献类型：
--
作者：
Bungartz, Gerd;Land, Hannah;Emerson, Stephen G.
HSC的功能依赖于对增殖的严格控制以及自我更新和分化之间的平衡。在这里，我们报告说，三聚体转录因子NF-Y是至关重要的生存周期，但不是静止的HSC。通过使用条件性基因敲除小鼠模型，我们证明了NF-Ya缺失导致HSC在G（2）/M中积累，并促进细胞凋亡，导致造血功能衰竭和动物死亡。这些缺陷伴随着影响细胞周期控制（细胞周期蛋白b1和p21），凋亡（Bcl-2）和自我更新（HoxB 4，Notch 1，Bmi-1）的多个基因的失调，并且独立于p53。我们的研究结果确定NF-Y作为一个关键的上游参与者在一个必要的监管网络的保存循环HSC。（血。2012; 119（6）：1380-1389）
HSC function depends on the tight control of proliferation and the balance between self-renewal and differentiation. Here, we report that the trimeric transcription factor NF-Y is critical for the survival of cycling, but not quiescent HSCs. With the use of a conditional knockout mouse model, we demonstrate that NF-Ya deletion creates an accumulation of HSCs in G(2)/M and prompts apoptosis, causing hematopoietic failure and death of the animal. These defects are accompanied by the dysregulation of multiple genes that influence cell cycle control (cyclin b1 and p21), apoptosis (Bcl-2), and self-renewal (HoxB4, Notch1, Bmi-1) and are independent of p53. Our results identify NF-Y as a pivotal upstream participant in a regulatory network necessary for the preservation of cycling HSCs. (Blood. 2012; 119(6): 1380-1389)