Cascades of transcriptional induction during dendritic cell maturation revealed by genome-wide expression analysis
Cascades of transcriptional induction during dendritic cell maturation revealed by genome-wide expression analysis
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DOI：
10.1096/fj.02-0724com
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发表时间：
2003-05-01
期刊：
影响因子：
4.8
通讯作者：
Hammer, J
中科院分区：
文献类型：
--
作者：
Türeci, Ö;Bian, HJ;Hammer, J
树突状细胞（DC）是免疫系统的中枢调节细胞。信号诱导的dc成熟被认为是特异性免疫应答的起点。为了进一步了解这一过程，我们利用Affymetrix基因芯片(R)分析了覆盖>6800个基因的转录物谱在CD40配体诱导的人髓系DCs成熟过程中的变化。除了重新发现与DC成熟相关的基因，证明所使用方法的可靠性外，我们还确定了簇蛋白作为新的成熟标记物。纵观整个时间过程，我们观察到不同功能基团分子的同步动力学，其时间共调节强调了树突状细胞成熟过程中已知的细胞事件。例如，炎症趋化因子的早期峰值波之后是组成性趋化因子的持续增加，并伴随着缓慢但持续的生存蛋白诱导。在细胞因子应答转录物立即但短暂的诱导后，一组基因的表达增加，这些基因不仅参与细胞因子作用的调节，而且还参与一般的转录。我们的研究结果表明，随着时间的推移，微阵列研究结合实时PCR不仅发现了具有功能意义的新标记分子，而且还剖析了生物过程的分子动力学，确定了复杂的调控途径。
Dendritic cells (DC) are central regulators of immunity. Signal-induced maturation of DCs is assumed to be the starting point for specific immune responses. To further understand this process, we analyzed the alteration of transcript profiles along the time course of CD40 ligand-induced maturation of human myeloid DCs by Affymetrix GeneChip(R) microarrays covering >6800 genes. Besides rediscovery of genes already described as associated with DC maturation proving reliability of the methods used, we identified clusterin as novel maturation marker. Looking across the time course, we observed synchronized kinetics of distinct functional groups of molecules whose temporal coregulation underscores known cellular events during dendritic cell maturation. For example, an early-peaking wave of inflammatory chemokines was followed by a sustained increase of constitutive chemokines and accompanied by slow but continuous induction of survival proteins. After an immediate but transient induction of cytokine-responsive transcripts, there was an increased expression of a group of genes involved in not only the regulation of cytokine effects, but also of transcription in general. Our results demonstrate that microarray studies along time courses combined with real-time PCR not only discover new marker molecules with functional implications, but also dissect the molecular kinetics of biological processes identifying complex pathways of regulation.