Dataset Information

Multi-OMICs analysis of metabolites, proteins, and histone modifications during human macrophage polarization reveals novel regulatory pathways

ABSTRACT: Macrophages are phagocytic cells in the innate immune system that infiltrate into resident tissues and subsequently polarize into at least two classical phenotypes: ‘pro-inflammatory’ M1 and ‘anti-inflammatory’ M2. Aberrant polarization can aggravate the pathophysiology of infectious diseases such as tuberculosis. Understanding the mechanisms that influence macrophage biology can lead to pharmacological control of polarization. We have developed a novel triomics approach utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) to perform simultaneous analysis of metabolites, proteins, and histone modifications. Using human blood derived monocytes that were polarized in vitro towards M1- (IFN-γ) and M2- (IL-4) phenotypes, we found that elevated nitric oxide production in M1 macrophages, inhibits oxidative phosphorylation and upregulates glycolytic pathways. Due to the uncoupling of glycolysis and the citric acid cycle/oxidative phosphorylation, an accumulation of acetylated amino acids was measured. Stable isotope tracing of glucose revealed reduced histone acetylation of certain key markers such as H3K27Ac, and others. We propose that the reduction could be due to trapping of excess acetyl-coA into acetylated amino acids. Furthermore, nitric oxide seems to irreversibly bind B12, a necessary co-factor for methionine synthase, inhibiting endogenous methionine synthesis, which could alter the histone epigenetic methylation and therefore downstream gene and protein expression. Triomics also allowed us to identify novel arginine methylation and Nα-acetylation of aspartate, glutamate, and ornithine. We conclude that triomics approach demonstrates a dynamic interplay between cellular metabolism and epigenetics and this axis can ultimately influence macrophage phenotype and gene expression.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood, Macrophage

DISEASE(S): Disease Free

SUBMITTER: Kangling Zhang

LAB HEAD: Kangling Zhang

PROVIDER: PXD030701 | Pride | 2022-10-13

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	M0M1M2_3days_TMT.msf	Msf
	M0M1M2_3days_TMT_fraction1_060321_rep1.raw	Raw
	M0M1M2_3days_TMT_fraction1_060321_rep2.raw	Raw
	M0M1M2_3days_TMT_fraction1_060321_rep3.raw	Raw
	M0M1M2_3days_TMT_fraction1_061521_rep1.raw	Raw

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Publications

Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization.

Sowers Mark L ML Tang Hui H Singh Vipul K VK Khan Arshad A Mishra Abhishek A Restrepo Blanca I BI Jagannath Chinnaswamy C Zhang Kangling K

The Journal of biological chemistry 20220827 10

Macrophages (MФ) are an essential immune cell for defense and repair that travel to different tissues and adapt based on local stimuli. A critical factor that may govern their polarization is the crosstalk between metabolism and epigenetics. However, simultaneous measurements of metabolites, epigenetics, and proteins (phenotype) have been a major technical challenge. To address this, we have developed a novel triomics approach using mass spectrometry to comprehensively analyze metabolites, prote ...[more]

PMID: 36030823

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