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Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk

ABSTRACT: Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk

PROVIDER: PRJNA329530 | ENA |

REPOSITORIES: ENA

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Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [ChIP_broadly]

Project description:The M1 and the M2 macrophage polarization programs (activated by IFNγ and IL-4, respectively) lie at the opposite edges of a continuum of activation states but are frequently co-activated during co-infections and in cancer despite controlling divergent functional responses. Whether these two programs are mutually exclusive, how they influence each other, and whether one represents the prevailing response, are all open questions. Co-administration of IFNγ and IL-4 exerted complex inhibitory effects over the M1 and M2 programs at the level of both epigenomic and transcriptional changes. Computational data mining and validation analyses revealed the molecular basis of the differential sensitivity of genes and cis-regulatory elements to the antagonistic effects of the opposite stimulus. For instance, while STAT1 and IRF motifs were associated with robust and IL-4-resistant responses to IFNγ, their coexistence with binding sites for some auxiliary transcription factors such as AP-1, generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation and the starting point for understanding macrophage responses in complex environmental conditions

2017-03-02 | GSE84519 | GEO

Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [ChIP_narrow]

2017-03-02 | GSE84518 | GEO

Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.

Project description: Not available

| S-EPMC5524187 | biostudies-literature

Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [RNA-Seq]

2017-03-02 | GSE84517 | GEO

Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-02 | GSE84520 | GEO

Mus musculus

Project description:Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [ChIP_narrow]

| PRJNA329536 | ENA

Mus musculus

Project description:Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [ChIP_broadly]

| PRJNA329535 | ENA

Mus musculus

Project description:Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [RNA-Seq]

| PRJNA329537 | ENA

Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells

Project description:Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells

| PRJNA675632 | ENA

High-throughput integration of metabolic and transcriptional profiles reveals major metabolic regulators of macrophage polarization

Project description:Macrophages polarize to divergent functional phenotypes depending on their microenvironment in a highly coordinated process of metabolic and transcriptional rewiring that is still poorly understood. We developed an Integrated Metabolomics and Gene Expression (IMAGE) profiling and analysis pipeline and applied it to extensively characterize global metabolic programs of macrophage polarization. IMAGE analysis identified 7 major (novel and known) regulatory modules responsible for metabolic rewiring during polarization, which we validated through extensive carbon and nitrogen labeling experiments. M1-specific modules included: inflammatory variant of the aspartate-arginosuccinate shunt; TCA cycle break at Idh expression accompanied by citrate accumulation and production of itaconate and fatty acid synthesis. In M2 macrophages we discovered significant role of glutamine in polarization, providing nitrogen for UDP-GlcNAc synthesis. Consistently, glutamine deprivation results in significant M2-specific defect in polarization. Our data provide, for the first time, a global view of the integrated transcriptional and metabolic changes that result in M1 and M2 polarization. Bone-marrow derived macrophages were generated from C57BL/6 mice were plated at ~100k cells per well in 96-well plate and stimulated with either Il4 or combination of LPS&IFNg or left unstimulated for 24 h mRNA was derived from lysates using Invitrogen oligo-dT beads

2014-05-30 | E-GEOD-53053 | biostudies-arrayexpress

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