The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice
The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice
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DOI：
10.1038/ng1938
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发表时间：
2007-02-01
期刊：
影响因子：
30.8
通讯作者：
Van Zant, Gary
中科院分区：
文献类型：
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作者：
Liang, Ying;Jansen, Michael;Van Zant, Gary
我们绘制了定量性状基因座，该定量特质基因座是造血细胞（HSC）数量变化的年轻成人C57BL/ 6（B6）和DBA/ 2（D2）小鼠之间的变化。在相互染色体3个同类小鼠中，由于增殖增强，自我更新和凋亡减少，渗透的D2等位基因增加了HSC数量，而B6等位基因的影响相反。使用寡核苷酸阵列，实时PCR和蛋白质印迹，我们鉴定了乳胶素（LXN），该基因的差分转录和表达与等位基因差异有关。表达与HSC的数量成反比。因此，使用逆转录病毒载体的LXN异位表达减少了干细胞种群的大小。我们确定了LXN转录启动位点上游的SNP簇，其中至少两个与调节干细胞的转录因子的潜在结合位点有关。因此，B6和D2等位基因之间的启动子多态性可能会影响LXN基因表达，从而影响造血干细胞的种群大小。
We mapped quantitative trait loci that accounted for the variation in hematopoietic stem cell ( HSC) numbers between young adult C57BL/6 ( B6) and DBA/ 2 ( D2) mice. In reciprocal chromosome 3 congenic mice, introgressed D2 alleles increased HSC numbers owing to enhanced proliferation and self-renewal and reduced apoptosis, whereas B6 alleles had the opposite effects. Using oligonucleotide arrays, real-time PCR and protein blots, we identified latexin ( Lxn), a gene whose differential transcription and expression was associated with the allelic differences. Expression was inversely correlated with the number of HSCs; therefore, ectopic expression of Lxn using a retroviral vector decreased stem cell population size. We identified clusters of SNPs upstream of the Lxn transcriptional start site, at least two of which are associated with potential binding sites for transcription factors regulating stem cells. Thus, promoter polymorphisms between the B6 and D2 alleles may affect Lxn gene expression and consequently influence the population size of hematopoietic stem cells.