PXD030701

PXD030701 is an original dataset announced via ProteomeXchange.

Title	Multi-OMICs analysis of metabolites, proteins, and histone modifications during human macrophage polarization reveals novel regulatory pathways
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:41:34.004.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kangling Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-04 01:20:50	ID requested
1	2022-10-13 07:18:16	announced
⏵ 2	2023-11-14 07:41:34	announced	2023-11-14: Updated project metadata.

Sowers ML, Tang H, Singh VK, Khan A, Mishra A, Restrepo BI, Jagannath C, Zhang K, Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization. J Biol Chem, 298(10):102418(2022) [pubmed]

submitter keyword: multi-omics.,Macrophage

Kangling Zhang
contact affiliation	University of Texas Medical Branch, Galveston, Texas, USA
contact email	kazhang@utmb.edu
lab head
Kangling Zhang
contact affiliation	University of Texas Medical Branch
contact email	kazhang@utmb.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030701
     1. Label: PRIDE project
     2. Name: Multi-OMICs analysis of metabolites, proteins, and histone modifications during human macrophage polarization reveals novel regulatory pathways