Dataset Information

Multiomics Analyses Reveal the Central Role of Pentose Phosphate Pathway in Resident Thymic Macrophages to Cope with Efferocytosis-Associated Stress

ABSTRACT: Tissue-resident macrophages (TRMs) are heterogeneous cell populations found throughout the body. Depending on their location, they perform diverse functions maintaining tissue homeostasis and providing immune surveillance. To survive and function within, TRMs adapt metabolically to the distinct microenvironments. However, little is known about the metabolic signatures of TRMs. The thymus provides a nurturing milieu for developing thymocytes yet efficiently removes those that failed the selection, relying on the TRMs – resident thymic macrophages (TMφs). This study harnesses multiomics analyses to characterize TMφs and unveils their unique metabolic features. We find that the pentose phosphate pathway (PPP) is preferentially activated in TMφs, responding to the reduction-oxidation demands associated with the efferocytosis of dying thymocytes. The blockade of PPP in Mφs leads to decreased efferocytosis, which can be rescued by ROS scavengers. Our study reveals the key role of PPP in TMφs and underscores the importance of metabolic adaptation in supporting Mφ efferocytosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE203543 | GEO | 2022/06/02

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Oxygen fluctuation during tissue remodeling imposes a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastomas are believed to possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. To identify adaptive response mechanism, we compared the effects of acute and chronic hypoxia versus oxygenation on stem-like glioblastoma (GS) cells. GS cell lines were established and propagated either under normoxia (21% O2) or hypoxia (1% O2) and subsequently exposed to acute normoxia or hypoxia, respectively. Gene expression profiling revealed that acute hypoxia predominantly induced metabolic pathways and cell cycle arrest, whereas chronic hypoxia activated neurodevelopmental processes. In particular, we found increased expression of glycolytic enzymes, especially of the preparatory phase of glycolysis, under acute hypoxia, whereas pentose phosphate pathway (PPP) enzymes were downregulated. The opposite was found for acute oxygenation of hypoxic GS cells. Findings were confirmed by qPCR and immunoblot analyses. Despite downregulation by hypoxia, expression of PPP enzymes is increased in GBMs compared to normal brain, whereas expression of hypoxia-inducible enzymes of the parallel preparatory phase of glycolysis is decreased. Immunohistochemistry revealed strong staining for PPP enzymes in the bulk of GBM tissue, especially in highly proliferative areas, but not in pseudopalisading (hypoxic) cells. Glycolytic enzymes displayed an inverse pattern. Mass spectrometric analysis using [1,2-13C2]-D-glucose showed reduced glucose flux through the PPP under hypoxia in favor of flux through glycolysis. Acute and chronic hypoxia increased cell migration but reduced proliferation, whereas normoxia had opposite effects. Our findings extend Warburg’s observations by showing that in most tumor cells the PPP, which supplies metabolites for biomass production, is favored over the parallel preparatory phase of glycolysis, but is suppressed under acute severe hypoxia, causing a switch to direct glycolysis to protect against hypoxic stress.

Dataset Information

Multiomics Analyses Reveal the Central Role of Pentose Phosphate Pathway in Resident Thymic Macrophages to Cope with Efferocytosis-Associated Stress

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets