Transcriptional profiling of macrophages derived from monocytes and iPS cells identifies a conserved response to LPS and novel alternative transcription.
Transcriptional profiling of macrophages derived from monocytes and iPS cells identifies a conserved response to LPS and novel alternative transcription.
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DOI：
10.1038/srep12524
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发表时间：
2015-07-30
影响因子：
4.6
通讯作者：
Gaffney DJ
中科院分区：
文献类型：
--
作者：
Alasoo K;Martinez FO;Hale C;Gordon S;Powrie F;Dougan G;Mukhopadhyay S;Gaffney DJ
从人诱导多能干细胞（IPSDMs）中分化出来的巨噬细胞在功能研究中是一种潜在的有价值的连接基因型和表型的新工具。然而，在全基因组水平上，这些细胞在很大程度上仍未被表征。在这里，我们使用RNA-Seq比较了naïve和脂多糖（LPS）刺激的单核细胞源性巨噬细胞（MDMs）和IPSDMs的转录组。IPSDM和MDM转录组大致相似，对LPS表现出高度保守的反应。然而，与抗原呈递和组织重塑相关的基因表达也存在显著差异。此外，编码参与中性粒细胞募集的多种趋化因子的基因在LPS刺激下在IPSDMs中表达更高。此外，通过分析个体转录物表达，鉴定出数百个基因在LPS处理后经历了替代启动子和3 '非翻译区使用，这代表了LPS反应中以前未被重视的调节水平。
Macrophages differentiated from human induced pluripotent stem cells (IPSDMs) are a potentially valuable new tool for linking genotype to phenotype in functional studies. However, at a genome-wide level these cells have remained largely uncharacterised. Here, we compared the transcriptomes of naïve and lipopolysaccharide (LPS) stimulated monocyte-derived macrophages (MDMs) and IPSDMs using RNA-Seq. The IPSDM and MDM transcriptomes were broadly similar and exhibited a highly conserved response to LPS. However, there were also significant differences in the expression of genes associated with antigen presentation and tissue remodelling. Furthermore, genes coding for multiple chemokines involved in neutrophil recruitment were more highly expressed in IPSDMs upon LPS stimulation. Additionally, analysing individual transcript expression identified hundreds of genes undergoing alternative promoter and 3′ untranslated region usage following LPS treatment representing a previously under-appreciated level of regulation in the LPS response.