Comparison of gene expression in CD34+ cells from bone marrow and G-CSF-mobilized peripheral blood by high-density oligonucleotide array analysis
Comparison of gene expression in CD34+ cells from bone marrow and G-CSF-mobilized peripheral blood by high-density oligonucleotide array analysis
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DOI：
10.1053/bbmt.2001.v7.pm11669215
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发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
Torok-Storb, B
中科院分区：
文献类型：
--
作者：
Graf, L;Heimfeld, S;Torok-Storb, B
一项前瞻性随机试验表明，接受粒细胞集落刺激因子（G-CSF）刺激的外周血单核细胞（GPBMC）的异基因移植受者与接受骨髓（BM）作为干细胞来源的受者相比，具有生存优势。这种优势的生物学基础尚不清楚，可能是由于移植的CD 34细胞、T细胞和/或单核细胞的定性和定量差异。为了开始解决这一问题，比较了从这2种干细胞来源分离的CD 34细胞中的基因表达模式，以鉴定可能区分这2个群体的功能途径。从多个健康供体的BM和外周血干细胞中分离CD 34细胞至纯度。(The完整的数据集将在出版后在http://parma.fhcrc.org/Igraf上提供。来自两种来源的合并样品的两种单独的RNA制备物通过Affytron寡核苷酸阵列芯片分析超过6400个人类基因的表达。样品之间的比较分析显示，与BM样品中的那些相比，在两种GPBMC样品中，一小组28个序列的表达增加，38个序列的表达减少超过3倍。更高表达的基因包括几个核蛋白和转录因子。功能分类的基因表达下降表明序列影响细胞周期的进展，与公认的静止循环CD 34细胞。还发现多种转录调节因子和趋化因子减少。这些数据强调，除了CD 34细胞数量增加外，G-CSF动员还导致显著的质的变化。它们是否影响植入仍有待确定。
A prospective randomized trial has shown that there is a survival advantage for allogeneic transplant recipients who received granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral blood mononuclear cells (GPBMC) versus those who received bone marrow (BM) as a source of stem cells. The biological basis for this advantage is not clear and may be attributable to qualitative as well as quantitative differences in the CD34 cells, T cells, and/or the monocytes transplanted. To begin to address this issue, gene expression patterns in CD34 cells isolated from these 2 stem cell sources were compared to identify functional pathways that may distinguish these 2 populations. CD34 cells were isolated to purity from the BM and peripheral blood stem cells of multiple healthy donors. (The complete data set mill be available at http://parma.fhcrc.org/Igraf upon publication.) Two separate RNA preparations from pooled samples from both sources were analyzed by Affymetrix Oligonucleotide Array chips for expression of over 6400 human genes. Comparative analyses among the samples showed that a small set of 28 sequences increased and 38 sequences decreased in expression more than 3-fold in both of the GPBMC samples compared to those in BM samples. More highly expressed genes include several for nuclear proteins and transcriptional factors. Functional categorization of the genes decreased in expression indicated sequences influential in cell cycle progression, in agreement with the recognized quiescence of circulating CD34 cells. Multiple transcriptional regulators and chemokines were also found to be decreased. These data emphasize that in addition to increased numbers of CD34 cells, G-CSF mobilization also results in significant qualitative changes. Whether they impact engraftment remains to be determined.