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表皮角质形成细胞对表皮生长因子反应的分析和荟萃分析。

Profiling and metaanalysis of epidermal keratinocytes responses to epidermal growth factor.

机构信息

The R. O. Perelman Department of Dermatology, Department of Biochemistry and Molecular Pharmacology, and the NYU Cancer Institute, NYU Langone Medical Center, 10016, New York, NY, USA.

出版信息

BMC Genomics. 2013 Feb 8;14:85. doi: 10.1186/1471-2164-14-85.

Abstract

BACKGROUND

One challenge of systems biology is the integration of new data into the preexisting, and then re-interpretation of the integrated data. Here we use readily available metaanalysis computational methods to integrate new data on the transcriptomic effects of EGF in primary human epidermal keratinocytes with preexisting transcriptomics data in keratinocytes and in EGF-treated non-epidermal cell types.

RESULTS

We find that EGF promotes keratinocyte proliferation, attachment and motility and, surprisingly, induces DUSPs that attenuate the EGF signal. Our metaanalysis identified overlapping effects of EGF with those of IL-1 and IFNγ, activators of keratinocyte in inflammation and wound healing. We also identified the genes and pathways suppressed by EGF but induced by agents promoting epidermal differentiation. Metaanalysis comparison with the EGF effects in other cell types identified extensive similarities between responses in keratinocytes and in other epithelial cell types, but specific differences with the EGF effects in endothelial cells, and in transformed, oncogenic epithelial cell lines.

CONCLUSIONS

This work defines the specific transcriptional effects of EGF on human epidermal keratinocytes. Our approach can serve as a suitable paradigm for integration of new omics data into preexisting databases and re-analysis of the integrated data sets.

摘要

背景

系统生物学的一个挑战是将新数据整合到已有的数据中,然后重新解释整合后的数据。在这里,我们使用现成的荟萃分析计算方法,将表皮角质形成细胞中 EGF 对转录组影响的新数据与角质形成细胞和 EGF 处理的非表皮细胞类型中的转录组数据进行整合。

结果

我们发现 EGF 促进角质形成细胞的增殖、附着和运动,令人惊讶的是,EGF 还诱导 DUSPs,从而减弱 EGF 信号。我们的荟萃分析发现 EGF 与 IL-1 和 IFNγ(炎症和伤口愈合中角质形成细胞的激活剂)的作用具有重叠性。我们还确定了 EGF 抑制但促进表皮分化的药物诱导的基因和途径。与其他细胞类型中 EGF 作用的荟萃分析比较,确定了角质形成细胞与其他上皮细胞类型之间反应的广泛相似性,但与内皮细胞和转化的、致癌的上皮细胞系中的 EGF 作用存在特定差异。

结论

这项工作定义了 EGF 对人类表皮角质形成细胞的特定转录效应。我们的方法可以作为将新的组学数据整合到已有数据库中并重新分析整合数据集的合适范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8041/3608085/4d150422b18b/1471-2164-14-85-1.jpg

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