Transcriptomics

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Transcriptome-based network analysis reveals a spectrum model of human macrophage activation [miRNA-seq]


ABSTRACT: Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease. Since transcriptional programs are further modulated on several levels including miRNAs we assessed the global spectrum of miRNA expression by miRNA-Seq in macrophages stimulated with IFNγ, IL4 or with the combination of TNFα, PGE2 and P3C

ORGANISM(S): Homo sapiens  

SUBMITTER: A Nino-Castro  T D Gohel   T C Freeman   M R Mallmann   W Krebs   A Draffehn   J L Schultze   J Sander   D De Nardo   H Theis   L Labzin   J Xue   L Schmidleithner   E Latz   H Ganesan   S V Schmidt   M Emde   I Quester   M Kraut   T Ulas   Joachim Schultze   M Beyer    

PROVIDER: E-GEOD-51307 | ArrayExpress | 2014-02-13

SECONDARY ACCESSION(S): SRP031496GSE51307PRJNA222999

REPOSITORIES: GEO, ArrayExpress, ENA

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Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization, and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a data set of 299 macrophage transcriptomes. Analysis of this data set revealed a spectrum of macrophage activation states extending the current M1  ...[more]

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