Dendritic cells (DC) represent professional antigen-presenting cells that develop from hematopoietic progenitors through successive steps of differentiation. Employing DNA microarray technology, we analysed the specific changes in gene expression that occur when human progenitor cells differentiate into DC. CD34 progenitor cells were first amplified in vitro with stem cell factor (SCF), Flt3 ligand (FL), thrombopoietin and IL-6/soluble IL-6 receptor fusion protein, and cells were then induced to differentiate into DC with IL-4 and GM-CSF. DC maturation was induced by TNFalpha. Progenitor cells and DC were subjected to transcriptional profiling by DNA microarrays that represent 13000 human genes. Our analysis revealed specific changes in the expression of a large number of cell surface antigens including molecules involved in antigen uptake and processing, cell migration and antigen presentation. Genes encoding such molecules were upregulated during DC differentiation as were genes encoding cytokines, cytokine receptors, chemokines and chemokine receptors. Stem cell genes and genes related to the multilineage differentiation potential and proliferative state of progenitor cells were downregulated. Our analysis also provides information on the expression profiles of transcriptional regulators such as the NF-kappaB/rel and STAT transcription factors. Interestingly, NF-kappaB/rel factors were found to be expressed in both progenitor cells and DC at similar levels and were induced by TNFalpha. In contrast, expression of STAT factors increased during DC differentiation and their expression was virtually unaffected by TNFalpha.

中文翻译：

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通过转录谱分析确定抗原呈递树突状细胞的分化程序。

树突状细胞（DC）代表从造血祖细胞通过连续分化步骤发展而来的专业抗原呈递细胞。利用DNA芯片技术，我们分析了当人类祖细胞分化为DC时基因表达的特定变化。首先用干细胞因子（SCF），Flt3配体（FL），血小板生成素和IL-6 /可溶性IL-6受体融合蛋白体外扩增CD34祖细胞，然后诱导细胞用IL-4和DC分化为DC。 GM-CSF。DC成熟由TNFα诱导。通过代表13000个人类基因的DNA微阵列对祖细胞和DC进行转录分析。我们的分析揭示了大量细胞表面抗原表达的特定变化，包括参与抗原摄取和加工，细胞迁移和抗原呈递的分子。编码此类分子的基因在DC分化过程中被上调，编码细胞因子，细胞因子受体，趋化因子和趋化因子受体的基因也被上调。下调干细胞基因以及与祖细胞的多系分化潜能和增殖状态有关的基因。我们的分析还提供了有关转录调节子（如NF-κB/ rel和STAT转录因子）表达谱的信息。有趣的是，发现NF-κB/ rel因子在祖细胞和DC中均以相似的水平表达，并由TNFα诱导。相反，