Transcriptional analysis of quiescent and proliferating CD34+human hemopoietic cells from normal and chronic myeloid leukemia sources
Transcriptional analysis of quiescent and proliferating CD34+human hemopoietic cells from normal and chronic myeloid leukemia sources
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DOI：
10.1634/stemcells.2007-0250
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Graham, Gerard J.
中科院分区：
文献类型：
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作者：
Graham, Susan M.;Vass, J. Keith;Graham, Gerard J.
静止期和分裂期造血干细胞（HSC）在外周循环和骨髓之间移动的能力存在显著差异。具体而言，长期植入潜力主要存在于静止的HSC亚组分中，并且G-CSF动员导致静止的HSC在外周中的优先积累。相反，来自慢性髓性白血病（CML）患者的干细胞在循环中显示组成性存在。为了理解这一点的分子基础，我们使用微阵列技术来分析分裂和静止，正常和CML衍生的CD 34+细胞之间的转录差异。我们的数据显示，正常和CML分裂细胞之间的显着的转录相似性，这表明BCR-ABL对CD 34+细胞转录组的影响比以前认为的更有限。此外，我们表明，静止的CML细胞更类似于他们的分裂的同行比静止的正常细胞是他们的。我们还表明这些转录差异反映在正常和CML CD 34+细胞的增殖活性改变。最令人感兴趣的是，与分裂细胞相比，在静止细胞中更丰富的主要类别的基因编码趋化因子家族的成员。我们提出了一个作用，表达的趋化因子静止HSC在编排的CD 34+细胞动员。
Quiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long-term engraftment potential predominantly resides in the quiescent HSC subfraction, and G-CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML-derived CD34+ cells. Our data show a remarkable transcriptional similarity between normal and CML dividing cells, suggesting that the effects of BCR-ABL on the CD34+ cell transcriptome are more limited than previously thought. In addition, we show that quiescent CML cells are more similar to their dividing counterparts than quiescent normal cells are to theirs. We also show these transcriptional differences to be reflected in the altered proliferative activity of normal and CML CD34+ cells. Of the most interest is that the major class of genes that is more abundant in the quiescent cells compared with the dividing cells encodes members of the chemokine family. We propose a role for chemokines expressed by quiescent HSC in the orchestration of CD34+ cell mobilization.