Microarray and serial analysis of gene expression analyses identify known and novel transcripts overexpressed in hematopoietic stem cells
Microarray and serial analysis of gene expression analyses identify known and novel transcripts overexpressed in hematopoietic stem cells
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DOI：
10.1158/0008-5472.can-03-3247
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发表时间：
2004-07-01
期刊：
影响因子：
11.2
通讯作者：
Civin, CI
中科院分区：
文献类型：
--
作者：
Georgantas, RW;Tanadve, V;Civin, CI
人CD 34（+）/CD 38（-）/Lin（-）细胞亚群约占CD 34（+）细胞群的1 -10%，含有少量原始造血祖细胞（HPC），但大多数是体内移植的原始造血干细胞（HSC）。我们分析了从正常成人供体骨髓、新生儿胎盘/脐带血和动员的成人供体外周血干祖细胞中分离的CD 34（+）/CD 38（-）/Lin（-）细胞群的基因表达。如通过Affyssin微阵列测量的，4746个基因在来自所有三种组织的CD 34（+）/CD 38（-）/Lin（-）细胞中表达。我们还测定了来自每个组织的干细胞耗尽、HPC富集的CD 34（+）/[CD 38/Lin]（++）细胞群的转录组。比较来自每个组织的CD 34（+）/CD 38（-）/Lin（-）（HSC富集）与CD 34（+）/[CD 38/Lin]（++）（HPC富集，HSC去除）细胞，得到81个基因过度表达和90个基因表达不足，这是所有三种CD 34（+）/CD 38（-）/Lin（-）细胞群共有的。这些转录物在来自所有三种组织的HSC中选择性表达，包括许多已知的基因（例如，转录因子、受体和信号分子），其可能在关键功能中起作用（例如，存活、自我更新、分化和/或迁移/粘附）。通过微阵列分析还检测到许多功能未知的基因/转录本。骨髓HSC和HPC群体的基因表达的系列分析证实了大多数过度表达的转录本的表达，其中检测到基因表达标签的可靠系列分析，并且还表明当前的微阵列不能检测到多达30%的HSC中表达的转录本，包括许多以前未知的转录本。这项工作是朝着完全定义正常人类HSC的转录组迈出的一步，并可能确定参与白血病发生和癌症干细胞的新基因。
The human CD34(+)/CD38(-)/Lin(-) cell subset, comprising similar to1-10% of the CD34(+) cell population, contains few of the less primitive hematopoietic (lineage-committed) progenitor cells (HPCs) but most of the primitive in vivo engrafting (lympho-)hematopoietic stem cells (HSCs). We analyzed gene expression in CD34(+)/CD38(-)/Lin(-) cell populations isolated from normal human adult donor bone marrow, neonatal placental/umbilical cord blood, and mobilized adult donor peripheral blood stem-progenitor cells. As measured by Affymetrix microarrays, 4746 genes were expressed in CD34(+)/CD38(-)/Lin(-) cells from all three tissues. We also determined the transcriptomes of the stem cell-depleted, HPC-enriched CD34(+)/[CD38/Lin](++) cell population from each tissue. Comparison of CD34(+)/CD38(-)/Lin(-) (HSC-enriched) versus CD34(+)/[CD38/Lin](++) (HPC-enriched, HSC-depleted) cells from each tissue yielded 81 genes overrepresented and 90 genes underrepresented, common to all three of the CD34(+)/CD38(-)/Lin(-) cell populations. These transcripts, which are selectively expressed in HSCs from all three tissues, include a number of known genes (e.g., transcription factors, receptors, and signaling molecules) that might play roles in key functions (e.g., survival, self-renewal, differentiation, and/or migration/adhesion) of human HSCs. Many genes/transcripts of unknown function were also detected by microarray analysis. Serial analysis of gene expression of the bone marrow HSC and HPC populations confirmed expression of most of the overrepresented transcripts for which reliable serial analysis of gene expression tags were detected and additionally suggested that current microarrays do not detect as many as 30% of the transcripts expressed in HSCs, including a number of previously unknown transcripts. This work is a step toward full definition of the transcriptome of normal human HSCs and may identify new genes involved in leukemogenesis and cancer stem cells.