Transcriptional profiling of macrophages derived from monocytes and iPS cells identifies a conserved response to LPS and novel alternative transcription

被引:75
作者
Alasoo, Kaur [1 ]
Martinez, Fernando O. [2 ]
Hale, Christine [1 ]
Gordon, Siamon [3 ]
Powrie, Fiona [4 ]
Dougan, Gordon [1 ]
Mukhopadhyay, Subhankar [1 ,3 ,4 ]
Gaffney, Daniel J. [1 ]
机构
[1] Wellcome Trust Sanger Inst, Hinxton, England
[2] Univ Oxford, Botnar Res Ctr NDORMS, Oxford, England
[3] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[4] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
GENE-EXPRESSION; STEM-CELLS; DIFFERENTIATION; PATTERNS; POLARIZATION; WIDESPREAD; ALIGNMENT; SEQUENCE; REVEALS; PROGRAM;
D O I
10.1038/srep12524
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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 naive 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.
引用
收藏
页数:12
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