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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.

Original publication

DOI

10.1038/srep12524

Type

Journal article

Journal

Scientific reports

Publication Date

30/07/2015

Volume

5

Addresses

Wellcome Trust Sanger Institute, Hinxton, UK.

Keywords

Monocytes, Cells, Cultured, Macrophages, Humans, Lipopolysaccharides, RNA, 3' Untranslated Regions, Chemokines, Gene Expression Profiling, Sequence Analysis, RNA, Promoter Regions, Genetic, Induced Pluripotent Stem Cells, Transcriptome