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Endothelial Cells Provide an Instructive Niche for the Differentiation and Functional Polarization of M2-like Macrophages

ABSTRACT: Endothelial cells and macrophages are known to engage in tight and specific interactions that contribute to the modulation of vascular function. Here we show that adult endothelial cells provide critical signals for the selective growth and differentiation of macrophages from several types of hematopoietic progenitor cells. The process features the formation of well-organized colonies that exhibit progressive differentiation from the center to the periphery and towards an M2-like phenotype, characterized by enhanced expression of Tie2 and CD206/Mrc1. These colonies are long-lived as long as the contact with the endothelium is maintained; removal of the endothelial monolayer results in rapid dissolution of the macrophage colonies. Not only the maintenance but also the formation of the colonies is strictly dependent on endothelial contact. We further found that M-CSF produced by the endothelium is critical for the expansion of the macrophage colonies and that blockade of M-CSF receptor impairs colony growth. Functional analyses indicate that these macrophages are capable of accelerating angiogenesis, promoting tumor growth and effectively engaging in tight associations with endothelial cells in vivo. These findings uncover a critical role of endothelial cells in the induction of macrophage differentiation and their ability to promote further polarization towards a proangiogenic phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE39660 | GEO | 2012/12/31

SECONDARY ACCESSION(S): PRJNA171351

REPOSITORIES: GEO

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Endothelial Cells Provide an Instructive Niche for the Differentiation and Functional Polarization of M2-like Macrophages

Project description:Endothelial cells and macrophages are known to engage in tight and specific interactions that contribute to the modulation of vascular function. Here we show that adult endothelial cells provide critical signals for the selective growth and differentiation of macrophages from several types of hematopoietic progenitor cells. The process features the formation of well-organized colonies that exhibit progressive differentiation from the center to the periphery and towards an M2-like phenotype, characterized by enhanced expression of Tie2 and CD206/Mrc1. These colonies are long-lived as long as the contact with the endothelium is maintained; removal of the endothelial monolayer results in rapid dissolution of the macrophage colonies. Not only the maintenance but also the formation of the colonies is strictly dependent on endothelial contact. We further found that M-CSF produced by the endothelium is critical for the expansion of the macrophage colonies and that blockade of M-CSF receptor impairs colony growth. Functional analyses indicate that these macrophages are capable of accelerating angiogenesis, promoting tumor growth and effectively engaging in tight associations with endothelial cells in vivo. These findings uncover a critical role of endothelial cells in the induction of macrophage differentiation and their ability to promote further polarization towards a proangiogenic phenotype. 8 samples were sequenced: bone marrow derived macrophages (BMDM) were stimulated with LPS, IL4, or none. Colony cells induced by endothelial cells for 7 days. Each was duplicated.

2012-12-31 | E-GEOD-39660 | biostudies-arrayexpress

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2023-11-23 | GSE246168 | GEO

Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF-and M-CSF-differentiated mouse macrophages

Project description:Macrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. In vitro macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1-and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM-and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for in vitro macrophage studies.

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Project description:Endothelial cells (ECs) not only form passive blood conduits. They actively contribute to nutrient transport and establish an instructive vascular niche to maintain and restore organ homeostasis. The role of the endothelium in the maintenance of muscle glucose homeostasis is however poorly understood. Here we show that, in skeletal muscle, the endothelial glucose transporter 1 (Glut1/Slc2a1) controls glucose uptake not via affecting transendothelial glucose transport, but via vascular niche control of muscle resident macrophages. Lowering endothelial glut1 via genetic depletion (glut1EC) or upon short-term high-fat diet increased angiocrine osteopontin (OPN/SPP1) secretion, promoting resident muscle macrophage activation and proliferation which impairs muscle insulin sensitivity. Consequently, co-deleting Spp1 from the endothelium prevented macrophage accumulation, reduced muscle OPN levels, and improved insulin sensitivity in glut1EC mice. Mechanistically, glut1-dependent endothelial glucose metabolic rewiring increased OPN in a serine metabolism-dependent fashion. Our data illustrate how the glycolytic endothelium creates a niche that controls resident muscle macrophage phenotype and function and directly links resident muscle macrophages to the development of muscle insulin resistance.

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Expression data from endothelial cells sorted from breast cancer cells MDA-MB231 as compared with normal endothelial cells

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Project description:This study aims to characterize the transcriptional profile of Granulocyte-macrophage colony-stimulating factor induced macrophages (GM-MÃ) and M-CSF macrophages (M-MÃ) and to investigate in situ a subset of genes and their products specific to each phenotype in human atherosclerosis plaques 18 RNG/MRC two-colour oligonucleotide microarrays (Le Brigand et al. 2006) were used to generate global mRNA expression profiles for GM-CSF-induced, M-CSF-induced, and peritoneal macrophages. The microarray experiments were conducted either as a common reference (peritoneal-like macrophages) design or using a direct design by hybridizing Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte-derived macrophage (GM-MÃ) and CSF-induced human monocyte-derived macrophages(M-MÃ) on the same arrays

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Expression data from endothelial cells sorted from breast cancer cells MDA-MB231 as compared with normal endothelial cells

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2013-12-31 | E-GEOD-48786 | biostudies-arrayexpress

STAT5 regulation of tumor associated macrophage function in murine models of breast cancer

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2021-11-17 | GSE171428 | GEO

Danger signal initiates differentiation of monocytes into osteopontin‑producing macrophages III

Project description:Purpose: We report the application of single-cell RNA sequencing for profiling the genexpression of different monocyte types in order to characterize monocytes that differentiate into macrophages under danger signal in comparison to conventional GM-CSF and M-CSF macrophages Methods: Monocytes freshly isolated from PBMCs were differentiated into GM-CSF, M-CSF, and danger-signal induced macrophages. Two million cells of each macrophage population were tagged accordingly with TotalSeq™‑B Hashtags. Single cell RNA sequencing was performed on all macrophage populations in order to characterize cells from each population. ScRNAseq analysis was performed with the R package Seurat on 16470 barcodes after filtering. Results: Cluster analysis reveals distinct separation of all three macrophage populations. Conclusion: The clear difference in overall gene expression profile suggests that macrophages exposed to danger signal differentiate into a novel macrophage type in contrast to conventional GM-CSF and M-CSF monocytes.

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