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 <i>in vitro</i> 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 <i>in vitro</i> 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-LPS<sub>early</sub>), LPS for 24 h (M-LPS<sub>late</sub>), 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 <i>in vivo</i> 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 <i>in vitro</i> macrophage activation states, built a classification model, and demonstrated the utility of the latter for <i>in vivo</i> macrophages.Meta-Analysis of <i>in vitro</i>-Differentiated Macrophages Identifies Transcriptomic Signatures That Classify Disease Macrophages <i>in vivo</i>.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 MPJrocher-Sheldon syndrome, macrophagocyte, multiple congenital arthrogryposis, fibrous ankylosis of multiple joints, Otto syndrome, arthrogryposis multiplex congenita, myodysplasia, congenital amyoplasia, typical plasmatocyte, amyoplasia congenita, AMC, monocyte-derived macrophage, Pl, congenital arthromyodysplasia, macrophage, lamellocyte, data., Guérin-Stern syndrome, Guerin-Stern syndrome, granulocyte, Rossi syndrome, Arthromyodysplasia congenita, histiocyte, podocyte, agranular plasmatocyte, myodystrophia fetalis deformansprojections, Oradexon, Materials, chronic obstructive pulmonary disease (COPD), Profiles, Rheumatoid arthritis NOS, Mast Cell Growth Factor 2, PPS1, B Cell Stimulatory Factor 1, Fat Pad, Rheumatoid disease, RhA - Rheumatoid arthritis, unspecified, hierarchy, macrophage, DmelCG12298, B-Cell Growth Factor-I, systematics, Chronic irreversible airway obstruction, SCRAMBLED, Fs(3)Hor, 16alpha-methyl-9alpha-fluoro-1-dehydrocortisol, 9-fluoro-11beta, 21-trihydroxy-16-methylpregna-1, Arthritis, OFC6, rheumatoid, (11beta, Tissue, Decaspray, CAFL - Chronic airflow limitation, CSIF-10, NTef2, Signatures, Expression Signature, disease (COPD), Pad, Homo sapiens disease, Methylfluorprednisolone, podocyte, chronic obstructive lung disease [Ambiguous], anatomical protrusion, typical plasmatocyte, obese, BCGF1, dexametasona, STRUBBELIG, Dexpak, Systematics, VWS1, monocyte-derived macrophage, not genetically inherited, Fs(3)Sz11, CHRONIC OBSTRUCTIVE AIRWAY DIS, BSF1, Zema-Pak, Expression Signatures, shelf, Obesity [Ambiguous], Corpuscles, simple tissue, fluormethylprednisolone, Airflow Obstruction, Expression Profile, 21-trihydroxy-16alpha-methylpregna-1, activation, Monocyte-Derived Macrophages, Decaject-L.A., Chronic Obstructive Airways Disease, Chronic obstructive lung disease, B-Cell Growth Factor-1, Hexadrol, macrophage polarization, Ozurdex, Cortisumman, 20-dione, Adiposity, Binetrakin, OBESITY NOS, projection, ridge, White Blood Cells, Monocyte-Derived Macrophage., Corpuscle, Ran/M1, 21-trihydroxy-16-methyl-, Material, OBSTRUCTIVE PULMONARY DISEASE (COPD), Calonat, Rheumatoid arthritis (disorder), CG2684, White, DexPak, Macrophage Activations, histiocyte, B Cell Stimulating Factor 1, Adipose, advanced, lamellae, CAO - Chronic airflow obstruction, obesity disease, CHRONIC OBSTRUCTIVE PULM DIS, Chronic obstructive pulmonary disease NOS, process of organ, Rheumatic gout, Chronic obstructive pulmonary disease finding, lamella, PULMONARY DISEASE (COPD), Fatty Tissue, Consensus, disease or disorder, Decaject, Decadron, Blood Corpuscle, agranular plasmatocyte, arthritis or polyarthritis, Aeroseb-Dex, 16alpha)-, Ly87, Chronic rheumatic arthritis, Activation, Profile, mei-1794, Rheumatoid arthritis NOS (disorder), Bone Marrow-Derived Macrophage, Expressions, Bone Marrow-Derived, CD284, Dexamethasone, Diodex, NEC, bodyfat, Chronic, progression of, Expression, B Cell Proliferating Factor, laminae, PIT, Toll, Auxiron, B Cell Growth Factor I, chronic obstructive airways disease NOS, anatomical process, Fat Pads, COAD, disorders, CSIF, COLD - Chronic obstructive lung disease, chronic, B Cell Growth Factor 1, Monocyte-Derived, autoimmune arthritis, chemical analysis, Gene Expression Signatures, BSF-1, condition, VWS, (COPD), chronic airway obstruction, 1-dehydro-16alpha-methyl-9alpha-fluorohydrocortisone, chronic obstructive, CAL - Chronic airflow limitation, organ process, Obesity (disorder), Macrophage, Pregna-1, Macrophages, Obesity NOS, Dub, ob, OB, IL10A, Lds, cytokine synthesis inhibitory factor, dexamethasone, processes, B-Cell Proliferating Factor, adipose, Gene Expression Profiles, White Blood, chronic obstructive lung disease (disorder), Bone Marrow-Derived Macrophages, B-Cell Stimulatory Factor 1, granulocyte, Decacort, White Blood Cell, chronic obstructive pulmonary disease, Azium, Il-4, 9-fluoro-11, determination, Feature, Chronic Airflow Obstructions, Gene Expression Profile, Pl, Adiposis, binetrakin, SUB, B-cell stimulatory factor 1, Classifications, Obese, hierarchies, 17, IL-4, diseases, Monocyte-Derived Macrophage, chronic obstructive airways disease NOS (disorder), RA, IL10X, diseases and disorders, Chronic Obstructive Pulmonary Disease (COPD), Arthritis or polyarthritis, fatty tissue, KIF20A, Cytokine Synthesis Inhibitory Factor, fat tissue, portion of tissue, Dexason, human disease, DmelCG2684, Pads, COLD (chronic obstructive lung disease), Gene Expressions, rheumatic, NEC in ICD9CM_2006, B-cell growth factor 1, PPS, Decameth, Decalix, Chronic airflow limitation, RA - Rheumatoid arthritis, pitrakinra, atrophic arthritis, MCGF-2, papilla, Transcriptomes, Consensus Development, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, B-Cell Stimulatory Factor-1, Rheumatoid, CHRONIC, obstructive lung disease, B-Cell Stimulating Factor-1, Expression Profiles, lamina, flanges, late, B Cell Stimulatory Factor-1, B-cell IgG differentiation factor, Lipopolysaccharide, 16alpha)-9-fluoro-11, Airflow Obstructions, IL10, Gene Expression, pulmonary disease (COPD), Taxonomies, Body Fat, Lipoglycans, CHRONIC OBSTRUCTIVE, Diseases, Dexacortal, chronic obstructive pulmonary disease and allied conditions, Obese (finding), precocious, tissue portion, Chronic airway disease, Millicorten, Genetic Materials, NOS, Genetic Material, TLR4, Rasl2-8, COPD NOS, Transcriptome Profiles, CHRONIC OBSTRUCTIVE LUNG DIS, 9alpha-fluoro-16alpha-methylprednisolone, Chronic airway obstruction, Blood Cell, Il4e12, Corson, cold, shelves, susceptibility to, White Blood Corpuscles, Features, early, 4-diene-3, Il-10, Chronic Airflow Obstruction, disease, Patient, spine, Horka, COPD - Chronic obstructive pulmonary disease, chronic obstructive airways disease, Fs(3)Horka, Decaject L.A., Activations, Cistron, Blood Corpuscles, BCGF-1, obstructive pulmonary disease (COPD), TGIF, Fat, Interferon, COLD, chronic obstructive lung disease, IGG1 induction factor, AT1G11140, other disease, Monocyte Derived Macrophages, Transcriptome Profile, taxonomy, DISEASE (COPD), Gene, fat, Development, White Blood Corpuscle, Hexadecadrol, CG12298, protrusion, Obesity, Pulmonary Disease, rheumatoid arthritis, IL-10, DmF2, Fatty, Interleukin 10, atrophic Arthritis, lod, study, Taxonomy, Genetic, LPS, Lps, lymphocyte stimulatory factor 1, Interleukin 4, ridges, Overweight and obesity, Chronic Obstructive, non-neoplastic, lipopolysaccharides, lamellocyte, Clients, IL4, disorder, SRF9, Characteristics, COPD, macrophagocyte, data, COAD - Chronic obstructive airways disease, Leukocyte, Transcriptome, Mast Cell Growth Factor-2, not elsewhere classified, Dexacortin, Monocyte Derived, medical condition, GVHDS, Cistrons, Client, PULM DIS CHRONIC OBSTRUCTIVE, obesity, Chronic obstructive pulmonary disease finding (finding), STRUBBELIG-RECEPTOR FAMILY 9, Characteristic, Dexasone, arthritis, Gene Expression Signature, Solurex, dexamethasonum, flange, obesity disorder, Proliferative arthritis, Maxidex, chronic obstructive airway disease, Blood Cells, Exhibit, Dops, Bone Marrow Derived Macrophages, Ran|M1, process, Cytokine formation-inhibiting factor (mouse clone F115 protein moiety reduced), Rheumatoid Arthritis, fatty depot, processus, cold (chronic obstructive lung disease), assay, Chronic Obstructive Lung Disease, Signature, T19D16.8, SCMother 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, Homo sapiens disease, diseases and disorders, Monocyte-Derived Macrophages, Macrophagedata.falseAMC Macrophage Data Access CommitteeData Access Committee EGAC00001001123EGAC00001001123960631921150EGAS00001003451EGAD00001004584