title: Transcriptional profiling of macrophages derived from monocytes and iPS cells identifies a conserved response to LPS and novel alternative transcription.
abstract: 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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Kaur
authors.initials: K
authors.lastname: Alasoo
authors.affiliation: Botnar Research Centre (NDORMS), University of Oxford, Oxford, UK.
authors.forename: Fernando O
authors.initials: FO
authors.lastname: Martinez
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Hale
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: 1] Wellcome Trust Sanger Institute, Hinxton, UK [2] Sir William Dunn School of Pathology, University of Oxford, Oxford, UK [3] Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gaffney
mesh_terms: D020413:3' Untranslated Regions; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D020413:3' Untranslated Regions; D018925:Chemokines; D008070:Lipopolysaccharides; D012313:RNA