EGAGenomicsMenno P.J. de Wintherhttps://ega-archive.org/dacs/EGAC00001001123EGAEGA DAC EGAC00001001123EGAm.dewinther@amc.uva.nlMacrophages 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.Meta-Analysis of in vitro-Differentiated Macrophages Identifies Transcriptomic Signatures That Classify Disease Macrophages in vivo.Chen Hung-Jen HJ, Li Yim Andrew Y F AYF, Griffith Guillermo R GR, de Jonge Wouter J WJ, Mannens Marcel M A M MMAM, Ferrero Enrico E, Henneman Peter P, de Winther Menno P J MPJother disease, human disease, Monocyte Derived Macrophages, Macrophages, disorders, Bone Marrow Derived Macrophages, Bone Marrow-Derived Macrophage, Monocyte Derived, medical condition, non-neoplastic, Bone Marrow-Derived, Monocyte-Derived Macrophage., disease, Monocyte-Derived, diseases, Bone Marrow-Derived Macrophages, Monocyte-Derived Macrophage, Diseases, disease or disorder, condition, disorder, diseases and disorders, Homo sapiens disease, Monocyte-Derived Macrophages, Macrophagerocher-Sheldon syndrome, macrophagocyte, fibrous ankylosis of multiple joints, Macrophage., Otto syndrome, congenital amyoplasia, Monocyte Derived Macrophages, Macrophages, typical plasmatocyte, amyoplasia congenita, Bone Marrow Derived Macrophages, Bone Marrow-Derived Macrophage, Monocyte Derived, monocyte-derived macrophage, Bone Marrow-Derived, Monocyte-Derived, macrophage, lamellocyte, Guérin-Stern syndrome, Guerin-Stern syndrome, Bone Marrow-Derived Macrophages, Monocyte-Derived Macrophage, granulocyte, Rossi syndrome, histiocyte, agranular plasmatocyte, myodystrophia fetalis deformans, Monocyte-Derived Macrophages, MacrophageOradexon, Azium, Materials, Il-4, 9-fluoro-11, determination, Feature, Chronic Airflow Obstructions, Gene Expression Profile, chronic obstructive pulmonary disease (COPD), Profiles, Mast Cell Growth Factor 2, PPS1, Adiposis, B Cell Stimulatory Factor 1, binetrakin, Fat Pad, SUB, B-cell stimulatory factor 1, Classifications, Obese, unspecified, hierarchies, 17, hierarchy, IL-4, diseases, macrophage, DmelCG12298, B-Cell Growth Factor-I, systematics, Monocyte-Derived Macrophage, chronic obstructive airways disease NOS (disorder), RA, Chronic irreversible airway obstruction, IL10X, diseases and disorders, SCRAMBLED, Chronic Obstructive Pulmonary Disease (COPD), Fs(3)Hor, fatty tissue, KIF20A, Cytokine Synthesis Inhibitory Factor, 16alpha-methyl-9alpha-fluoro-1-dehydrocortisol, fat tissue, Dexason, human disease, DmelCG2684, Pads, COLD (chronic obstructive lung disease), Gene Expressions, 21-trihydroxy-16-methylpregna-1, NEC in ICD9CM_2006, B-cell growth factor 1, OFC6, (11beta, Tissue, PPS, Decaspray, Decameth, CAFL - Chronic airflow limitation, 25-153, CSIF-10, NTef2, Signatures, Decalix, Chronic airflow limitation, pitrakinra, Expression Signature, disease (COPD), MCGF-2, Transcriptomes, cleft lip and/or palate with mucous cysts of lower lip, Chronic Obstructive Pulmonary Diseases, Pad, Homo sapiens disease, Consensus Development, Methylfluorprednisolone, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, B-Cell Stimulatory Factor-1, CHRONIC, chronic obstructive lung disease [Ambiguous], obstructive lung disease, anatomical protrusion, typical plasmatocyte, obese, B-Cell Stimulating Factor-1, Expression Profiles, BCGF1, dexametasona, STRUBBELIG, Dexpak, Systematics, B Cell Stimulatory Factor-1, VWS1, B-cell IgG differentiation factor, Lipopolysaccharide, monocyte-derived macrophage, not genetically inherited, 16alpha)-9-fluoro-11, Airflow Obstructions, Fs(3)Sz11, IL10, Gene Expression, CHRONIC OBSTRUCTIVE AIRWAY DIS, pulmonary disease (COPD), BSF1, Taxonomies, Body Fat, Lipoglycans, Zema-Pak, Chronic Obstructive Airway Disease, Expression Signatures, CHRONIC OBSTRUCTIVE, Diseases, Dexacortal, chronic obstructive pulmonary disease and allied conditions, Obesity [Ambiguous], Obese (finding), Corpuscles, Chronic airway disease, Millicorten, Genetic Materials, NOS, simple tissue, Rheumatoid arthritis, fluormethylprednisolone, Airflow Obstruction, Expression Profile, Genetic Material, activation, Monocyte-Derived Macrophages, Rasl2-8, COPD NOS, Transcriptome Profiles, Decaject-L.A., CHRONIC OBSTRUCTIVE LUNG DIS, 9alpha-fluoro-16alpha-methylprednisolone, Chronic Obstructive Airways Disease, Chronic airway obstruction, Blood Cell, Chronic obstructive lung disease, B-Cell Growth Factor-1, Hexadrol, Il4e12, macrophage polarization, Corson, cold, Cortisumman, Ozurdex, susceptibility to, 20-dione, Adiposity, Binetrakin, OBESITY NOS, White Blood Corpuscles, Features, early, 4-diene-3, White Blood Cells, Il-10, Monocyte-Derived Macrophage., Chronic Airflow Obstruction, Corpuscle, disease, Ran/M1, 21-trihydroxy-16-methyl-, Patient, Material, spine, OBSTRUCTIVE PULMONARY DISEASE (COPD), Horka, COPD - Chronic obstructive pulmonary disease, Calonat, chronic obstructive airways disease, CG2684, Fs(3)Horka, Decaject L.A., Activations, White, DexPak, Cistron, Macrophage Activations, Blood Corpuscles, BCGF-1, histiocyte, obstructive pulmonary disease (COPD), TGIF, Fat, Interferon, chronic obstructive lung disease, COLD, B Cell Stimulating Factor 1, IGG1 induction factor, AT1G11140, Adipose, other disease, Monocyte Derived Macrophages, Transcriptome Profile, taxonomy, DISEASE (COPD), CAO - Chronic airflow obstruction, obesity disease, Gene, UniProtKB:P05112-1, CHRONIC OBSTRUCTIVE PULM DIS, fat, Development, Chronic obstructive pulmonary disease NOS, White Blood Corpuscle, Hexadecadrol, CG12298, protrusion, Chronic obstructive pulmonary disease finding, Obesity, PULMONARY DISEASE (COPD), Pulmonary Disease, Fatty Tissue, rheumatoid arthritis, IL-10, Consensus, disease or disorder, lip pit syndrome, DmF2, Decaject, Fatty, Interleukin 10, Decadron, Blood Corpuscle, agranular plasmatocyte, Aeroseb-Dex, lod, study, Taxonomy, 16alpha)-, Ly87, Genetic, Activation, Profile, LPS, Lps, mei-1794, lymphocyte stimulatory factor 1, Interleukin 4, Bone Marrow-Derived Macrophage, Overweight and obesity, Chronic Obstructive, Expressions, non-neoplastic, Bone Marrow-Derived, lipopolysaccharides, Diodex, lamellocyte, Clients, NEC, IL4, bodyfat, disorder, Chronic, SRF9, Expression, Characteristics, B Cell Proliferating Factor, PIT, Chronic Obstructive Pulmonary Disease, COPD, macrophagocyte, Auxiron, COAD - Chronic obstructive airways disease, Leukocyte, Transcriptome, Mast Cell Growth Factor-2, B Cell Growth Factor I, chronic obstructive airways disease NOS, not elsewhere classified, Fat Pads, COAD, disorders, Dexacortin, CSIF, Monocyte Derived, medical condition, GVHDS, COLD - Chronic obstructive lung disease, Cistrons, Client, chronic, PULM DIS CHRONIC OBSTRUCTIVE, obesity, Chronic obstructive pulmonary disease finding (finding), B Cell Growth Factor 1, STRUBBELIG-RECEPTOR FAMILY 9, Monocyte-Derived, Characteristic, Dexasone, chemical analysis, Gene Expression Signatures, BSF-1, condition, VWS, Gene Expression Signature, (COPD), Solurex, chronic airway obstruction, 1-dehydro-16alpha-methyl-9alpha-fluorohydrocortisone, chronic obstructive, dexamethasonum, CAL - Chronic airflow limitation, obesity disorder, Obesity (disorder), Macrophage, Maxidex, chronic obstructive airway disease, Blood Cells, Pregna-1, Exhibit, Macrophages, Dops, Obesity NOS, Dub, ob, OB, Bone Marrow Derived Macrophages, IL10A, Ran|M1, Lds, cytokine synthesis inhibitory factor, dexamethasone, Cytokine formation-inhibiting factor (mouse clone F115 protein moiety reduced), Rheumatoid Arthritis, B-Cell Proliferating Factor, fatty depot, adipose, Gene Expression Profiles, White Blood, chronic obstructive lung disease (disorder), Bone Marrow-Derived Macrophages, B-Cell Stimulatory Factor 1, granulocyte, cold (chronic obstructive lung disease), assay, Chronic Obstructive Lung Disease, Signature, Decacort, T19D16.8, White Blood Cell, SCM, chronic obstructive pulmonary diseasefalseAMC Macrophage Data Access CommitteeData Access Committee EGAC000010011232025-1-9EGAC00001001123960631921150EGAS00001003451EGAD00001004584