Differential expression between WT and AhRR fetal liver macrophages
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE254369 | GEO | 2024/06/04
REPOSITORIES: GEO
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Project description:Differential expression between WT and AhRR fetal liver macrophages
| PRJNA1070258 | ENA
Project description:Background: Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a hematopoietic growth factor and adjuvant in cancer immunotherapy via stimulation of dendritic cells/APCs. However, GM-CSF has yielded inconsistent results and its role regarding in vivo modulation of macrophages remains underexplored. We previously demonstrated that 100ng “high-dose” intratumor (IT) GM-CSF ablated tumor blood vessels and worsened tumor hypoxia after 3 weeks through tumor-associated macrophage (TAM) soluble VEGFR-1 production in PyMT murine breast cancer. Here, we investigate a role for “low-dose” IT GM-CSF on tumor oxygen and the impact on immunotherapy response, TAMs/myeloid cells, and TILs relative to “high-dose”. Methods: We performed IT injections of dose-specific GM-CSF or saline controls and then evaluated phenotypic effects after 3 weeks. We used Electron Paramagnetic Resonance Oximetry to measure and image in vivo tumor oxygen in real-time, and fluorescent immunohistochemistry to assess tumor blood vessels. IT GM-CSF doses were tested in priming PyMT tumors for sensitization to PD1. We performed RNA Sequencing of TAM and CD8 TIL to observe transcriptional changes coupled with flow cytometry of peripheral blood monocytes, tumor myeloid, and TIL populations in immunology cold" PyMT tumors response to dose-optimized GM-CSF. Lastly, we assessed and compared effects of IT GM-CSF on TAM and TIL in an immunologically “hot” 4T1 breast cancer model. Results: 5ng IT GM-CSF significantly increased PyMT tumor oxygen without augmenting tumor growth and promoted tumor vessel health via increased pericyte coverage. Priming of PyMT tumors with 5ng IT GM-CSF (“low-dose”, hypoxia reduced) sensitized “cold” PyMT tumors to PD1, but this synergy was not observed with 100ng (“high-dose”, hypoxia exacerbated). Immunologically, 5ng GM-CSF did not increase monocyte mobilization or alter phenotypic marker expression on TAMs, but reduced hypoxic and inflammatory transcriptional programs in macrophages and CD8 TIL isolated from PyMT tumors. 100ng increased infiltration of myeloid cells and TAMs but these TAMs had reduced MHCII expression, suggesting support of immune-suppressive TAM under hypoxia. Some tumors exhibited increased CD8 polyfunctionality either dose suggesting mild CD8 TIL priming. On the other hand, 100ng in “hot” 4T1 tumors resulted in increased TAM MHCII and other immunostimulatory molecules with moderate increases in CD8 TIL polyfunctionality and exhausted PD1hiTIM3+ phenotype, indicating that GM-CSF may have opposing effects on macrophage modulation based on tumor immunological status.
2023-09-12 | GSE228874 | GEO
Project description:Bone marrow cells were isolated, primed with M-CSF (M-BMDM) or GM-CSF (GM-BMDM) and cultured for 7 days. The proteomic difference between GM-BMDM and M-BMDM were analyzed to describe the phenotye and function of two types of macrophages.
2023-03-29 | PXD041180 |
Project description:Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs upregulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs.
2015-08-04 | PXD002582 | Pride
Project description:Bone marrow cells (BM) were isolated and primed with M-CSF (M BMDM) or GM-CSF (GM BMDM) for 7 days. M-BMDMs were treated with IL6 (20 ng/ml) for 3 h or 24 h while GM-BMDMs were treated for 3 h. The difference between BM, M-BMDM, and GM-BMDM were analyzed to describe the phenotye and function of each population. Moreover, by RNA-seq analysis, the influence of IL6 treatment on GM-BMDMs and M-BMDMs were analyzed.
2022-10-31 | GSE179637 | GEO
Project description:By employing miRCURY LNAM-bM-^DM-" microRNA Array, we have identified a subset of 21 top miRNAs that are differentially expressed between GM-BMM and M-BMM cells To know the differential expression of miRNA in mouse GM-CSF-induced bone marrow-derived macrophages (GM-BMM) vs. M-CSF-induced BMM (M-BMM)
2013-04-17 | E-GEOD-46085 | biostudies-arrayexpress
Project description:GM-CSF paradoxically possesses ability to differentiate both classically activated macrophages (MØs) with dominant proinflammatory function (M1-like MØs) and alternative activated MØs with strong immunosuppressive function (M2-like MØs). The intrinsic regulatory mechanism responsible for functional polarization of MØs under GM-CSF signalling remains elusive. Here we revealed that cytokine-inducible SH2-containing protein (CIS), induced by GM-CSF, is a key determinant in controlling MØ polarization. Compared to WT MØs, Cish-/- MØs gained characteristics of alternative activated MØs (M2 MØs), showing high expression of prototypic M2 markers Arginase 1, Tgm2 and YM-1; strong suppression of T cell proliferation; and low production of IL-12 and other proinflammatory cytokines¬¬. Differing from canonical IL-4/STAT6/IRF4 signaling axis of M2 induction, development of M2 MØ characteristics in Cish-/- MØs was associated with intensified STAT5 activation and consequent IRF8 downregulation. Attenuation of GM-CSF signalling via JAK inhibition and IRF8 rescue corrected certain functional defects in Cish-/- MØs. As CIS inhibition in NK and T cells promotes anti-tumour immunity, we showed that CIS deficiency enhanced the development of intra-tumoural M2 MØs and reduced CTL induction within tumour microenvironment with elevated GM-CSF. Overall, we conclude that CIS acts as an intrinsic rheostat to control intense GM-CSF signalling in order to maintain proinflammatory functions of MØs. Targeting CIS as a checkpoint in cancer immunotherapy should consider its role in regulating myeloid cell function.
2023-01-21 | PXD018390 | Pride
Project description:Comparison of the transcriptome macrophages derived from CD14+ human monocyte-derived macrophages generated in the presence of M-CSF (M-Mphage) or GM-CSF (GM-Mphage) and MTX.
2023-06-14 | GSE228475 | GEO
Project description:Comparison of the transcriptome of CD14+ human monocytes and CD14+ human monocyte-derived macrophages generated in the presence of M-CSF (M-MØ) or GM-CSF (GM-MØ).
2022-03-24 | GSE188278 | GEO
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
2010-05-16 | E-GEOD-18275 | biostudies-arrayexpress