p53 Regulates Hematopoietic Stem Cell Quiescence . Mus musculus

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. Overall design: RNAs isolated from wild type, p53 -/- and p53 -/- Mef -/- LSK cells were used in oligonucleotide arrays (Affymetrix)

p53蛋白（p53 protein）在DNA损伤细胞应答中的重要性已广为人知，但其在稳态造血过程中的功能尚未阐明。本研究明确了p53在调控造血干细胞（hematopoietic stem cells, HSCs）静息状态中的关键作用，尤其在促进缺乏MEF/ELF4转录因子的造血干细胞（HSCs）所呈现的增强型静息状态方面。对从野生型及p53基因敲除小鼠中分离的造血干细胞（HSCs）进行转录谱分析，鉴定出Gfi-1与Necdin为p53的靶基因；通过慢病毒载体上调或敲低这两个基因的表达，本研究证实了其在调控造血干细胞静息状态中的重要性。明确p53（及其靶基因）在控制造血干细胞细胞周期进入中的作用，或可开发出能够清除静息态癌症（干）细胞的治疗策略。总体设计：将从野生型、p53基因敲除（p53 -/-）以及p53与MEF双基因敲除（p53 -/- Mef -/-）的LSK细胞中分离得到的RNA，用于寡核苷酸芯片（Affymetrix）检测。