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Front Immunol. 2019 Dec 11;10:2887. doi: 10.3389/fimmu.2019.02887. eCollection 2019.

Meta-Analysis of in vitro-Differentiated Macrophages Identifies Transcriptomic Signatures That Classify Disease Macrophages in vivo.

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Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
Genome Diagnostics Laboratory, Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
Epigenetics Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom.
Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
Computational Biology, Target Sciences, GlaxoSmithKline, Stevenage, United Kingdom.
Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University, Munich, Germany.


Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage models to perform a meta-analysis. Specifically, we obtained gene expression data from unstimulated macrophages (M0) and macrophages stimulated with lipopolysaccharides (LPS) for 2-4 h (M-LPSearly), LPS for 24 h (M-LPSlate), LPS and interferon-γ (M-LPS+IFNγ), IFNγ (M-IFNγ), interleukin-4 (M-IL4), interleukin-10 (M-IL10), and dexamethasone (M-dex). Our meta-analysis identified consistently differentially expressed genes that have been implicated in inflammatory and metabolic processes. In addition, we built macIDR, a robust classifier capable of distinguishing macrophage activation states with high accuracy (>0.95). We classified in vivo macrophages with macIDR to define their tissue- and disease-specific characteristics. We demonstrate that alveolar macrophages display high resemblance to IL10 activation, but show a drop in IFNγ signature in chronic obstructive pulmonary disease patients. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but acquired LPS-activation features in diabetic-obese patients. Rheumatoid arthritis synovial macrophages exhibit characteristics of IL10- or IFNγ-stimulation. Altogether, we defined consensus transcriptional profiles for the eight in vitro macrophage activation states, built a classification model, and demonstrated the utility of the latter for in vivo macrophages.


adipose tissue macrophages (ATMs); alveolar macrophages (AMs); elastic net classification; macrophage identifier (macIDR); macrophages; meta-analysis; synovial macrophages (SMs)

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