p53 regulates hematopoietic stem cell quiescence.

p53 regulates hematopoietic stem cell quiescence.
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DOI:
10.1016/j.stem.2008.11.006
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发表时间:
2009-01-09
期刊:
影响因子:
23.9
通讯作者:
Nimer SD
Nimer SD
中科院分区:
医学1区
文献类型:
--
作者:
Liu Y;Elf SE;Miyata Y;Sashida G;Liu Y;Huang G;Di Giandomenico S;Lee JM;Deblasio A;Menendez S;Antipin J;Reva B;Koff A;Nimer SD

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p53蛋白在细胞对DNA损伤反应中的重要性是众所周知的,但其在稳态造血过程中的功能尚未确定。我们已经确定了p53在调节造血干细胞静止中的关键作用,特别是在缺乏MEF/ELF4转录因子的造血干细胞中促进增强的静止。从野生型和p53缺失小鼠分离的HSC转录分析发现,Gfi-1和Necdin是p53的靶基因,并利用慢病毒载体上调或敲低这些基因的表达,我们发现它们在调节HSC静止中的重要作用。确定p53(及其靶基因)在控制造血干细胞细胞周期进入中的作用,可能会导致能够消除静止癌症(干细胞)的治疗策略。
The importance of the p53 protein in the cellular response to DNA damage is well known, but its function during steady-state hematopoiesis has not been established. We have defined a critical role of p53 in regulating hematopoietic stem cell quiescence, especially in promoting the enhanced quiescence seen in HSCs that lack the MEF/ELF4 transcription factor. Transcription profiling of HSCs isolated from wild type and p53 null mice identified Gfi-1 and Necdin as p53 target genes and using lentiviral vectors to upregulate or knockdown the expression of these genes, we show their importance in regulating HSC quiescence. Establishing the role of p53 (and its target genes) in controlling the cell cycle entry of HSCs may lead to therapeutic strategies capable of eliminating quiescent cancer (stem) cells.
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