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

Chen, Hung-Jen; Li Yim, Andrew Y. F.; Griffith, Guillermo R.; de Jonge, Wouter J.; Mannens, Marcel M. A. M.; Ferrero, Enrico; Henneman, Peter und de Winther, Menno P. J. (11. Dezember 2019): Meta-Analysis of in vitro-Differentiated Macrophages Identifies Transcriptomic Signatures That Classify Disease Macrophages in vivo. In: Frontiers in Immunology, Bd. 10, 2887: S. 1-15

Abstract

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-gamma (M-LPS+IFN gamma), IFN gamma (M-IFN gamma), 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 IFN gamma 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 IFN gamma-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.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Keywords: Meta-analysis; elastic net classification; macrophages; alveolar macrophages (AMs); synovial macrophages (SMs); adipose tissue macrophages (ATMs); macrophage identifier (macIDR)
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1664-3224
• Sprache: Englisch