Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1079493 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metastasis is the major cause of cancer-related mortality. In the lung metastasis, monocyte-derived macrophages (Mo-macs) exhibit a complex function. However, tumor cells how to derive lung metastasis through Mo-macs remains unclear. Here we show that a tumor-secreted protein osteoprotegerin (OPG) contributes to the lung metastasis of cancer depends on the Mo-macs by an in vivo screening. OPG binds with RANKL to block the signaling between RANKL-RANK on Mo-macs. RANKL-RANK signals induce Mo-macs to secrete CXCL10, recruiting NK cells to control the lung metastasis. Increased expression of OPG in the metastases is regulated by TGF-β. Consistent with our findings, enrichment of OPG amplifications was observed in metastatic cancer patients, and increased expression of OPG was also shown in the lung metastatic sites compared with the paired primary breast cancer samples. Overall, our findings reveal a mechanism of how tumor cells promote lung metastasis via inhibiting the function of Mo-macs.
2024-12-16 | GSE260469 | GEO
Project description:Metastasis is the major cause of cancer-related mortality. In the lung metastasis, monocyte-derived macrophages (Mo-macs) exhibit a complex function. However, tumor cells how to derive lung metastasis through Mo-macs remains unclear. Here we show that a tumor-secreted protein osteoprotegerin (OPG) contributes to the lung metastasis of cancer depends on the Mo-macs by an in vivo screening. OPG binds with RANKL to block the signaling between RANKL-RANK on Mo-macs. RANKL-RANK signals induce Mo-macs to secrete CXCL10, recruiting NK cells to control the lung metastasis. Increased expression of OPG in the metastases is regulated by TGF-β. Consistent with our findings, enrichment of OPG amplifications was observed in metastatic cancer patients, and increased expression of OPG was also shown in the lung metastatic sites compared with the paired primary breast cancer samples. Overall, our findings reveal a mechanism of how tumor cells promote lung metastasis via inhibiting the function of Mo-macs.
2024-12-16 | GSE259293 | GEO
Project description:Monocytes are ephemeral myeloid immune cells that arise from adult hematopoiesis and circulate in the blood. They comprise two main subsets, in mice defined as classical and non-classical monocytes (CM, NCM). Recent fate mapping and transcriptomic analyses revealed that CM themselves are heterogeneous. Here, we report surface markers that allow segregation of murine GMP- and MDP-derived CM, as well as their functional characterization, including fate definition following adoptive cell transfer. GMP-Mo and MDP- Mo gave equal rise to homeostatic CM progeny, such as blood NCM and gut macrophages; the cells however differentially seeded selected other tissues, including the dura mater and lung. Specifically, GMP-Mo and MDP-Mo gave rise to distinct interstitial lung macrophages, linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide evidence for the existence of two functionally distinct CM subsets in the mouse, which differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge.
2024-05-04 | GSE261003 | GEO
Project description:Ribosome profiling (Ribo-Seq) (maps positions of translating ribosomes on the transcriptome) and RNA-Seq (quantifies the transcriptome) analysis of Rattus norvegicus cells infected with Moloney Murine Leukemia Virus (Mo-MuLV).
2018-01-17 | E-MTAB-6231 | biostudies-arrayexpress
Project description:Monocytes can differentiate into macrophages or dendritic cells. When treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) monocytes differentiate into macrophage-like cells. Here, we report that pharmacological blockade of the nuclear receptor PPARγ in monocytes turns GM-CSF into a potent inducer of dendritic cell (Mo-DC) differentiation. Remarkably, simultaneous blockade of PPARγ and mTORC1 in the presence of GM-CSF promoted the differentiation of Mo-DCs with a stronger phenotypic stability and immunogenic profile when compared with canonical Mo-DCs differentiated by treatment with GM-CSF and IL-4. Moreover, and in contrast with the observations made with GM-CSF and IL-4, blockade of PPARγ and mTORC1 was shown to be able to induce the differentiation of monocyte-derived macrophages (Mo-Macs) into Mo-DCs. Transcriptional profiling performed at either early time points, as well as at the end of the differentiation process, revealed marked differences in the gene expression signature between Mo-DCs induced by GM-CSF and IL-4 and Mo-DCs induced by GM-CSF in the presence of PPARγ and/or mTORC1 inhibitors, thus suggesting diverging differentiation pathways. Our observations might contribute, not only to a better understanding of the mechanisms involved in Mo-DCs differentiation but also to improving the efficacy of both, DC vaccines and therapies focusing on the modulation of myeloid cell functions.
2023-02-23 | GSE210935 | GEO
Project description:Monocytes are short-lived myeloid immune cells that arise from adult hematopoiesis and circulate for a short time in the blood. They comprise two main subsets, in mice defined as classical Ly6Chigh and non-classical Ly6Clow monocytes (CM, NCM). Recent fate mapping and transcriptomic analyses revealed that CM themselves are heterogeneous. Here, we report surface markers that allow segregation of murine GMP- and MDP-derived CM in the BM and blood. Functional characterization, including fate definition following adoptive cell transfer, established that GMP-Mo and MDP-Mo could equal rise to homeostatic CM progeny, such as NCM in blood and gut macrophages, but differentially seeded selected other tissues. Specifically, GMP-Mo and MDP-Mo gave rise to distinct interstitial lung macrophages, thus linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide comprehensive evidence for the existence of two functionally distinct CM subsets in the mouse, which differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge. Our findings are indicative of impact of monocyte ontogeny on in situ differentiation.
2024-05-04 | GSE261594 | GEO
Project description:Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To identify non-invasive miRNA biomarkers, miRNA profiling was performed in blood samples collected from MWCNT exposed mice.
2019-07-26 | GSE130109 | GEO
Project description:Pulmonary fibrosis is an incurable disease, which increasingly manifests with advanced age. Yet, how the ageing hematopoietic niche influences immune cell function and fibrosis progression in the lungs remains elusive. Using heterochronic transplant mouse models, we discovered that an aged bone marrow exacerbates lung fibrosis irrespective of lung tissue age. Upon lung injury, there was an increased pulmonary infiltration of monocyte-derived alveolar macrophages (Mo-AMs) from an aged bone marrow. These Mo-AMs displayed an enhanced profibrotic profile and a delayed transition in acquiring a homeostatic tissue-resident phenotype. This impaired Mo-AM differentiation was attributed to diminished numbers of regulatory T cells (Tregs) and the reduced availability of the anti-inflammatory cytokine IL-10 in the lung microenvironment of mice engrafted with aged bone marrow. Mechanistically, we show that Tregs are crucial providers of IL-10 that promote timely Mo-AM maturation and attenuate fibrosis progression. Our findings demonstrate the critical influence of an aged bone marrow on the development of lung fibrosis and identify a Treg-mediated resolutory axis as a potential therapeutic target for accelerated tissue repair.
2024-12-16 | GSE277799 | GEO
Project description:Pulmonary fibrosis is an incurable disease, which increasingly manifests with advanced age. Yet, how the ageing hematopoietic niche influences immune cell function and fibrosis progression in the lungs remains elusive. Using heterochronic transplant mouse models, we discovered that an aged bone marrow exacerbates lung fibrosis irrespective of lung tissue age. Upon lung injury, there was an increased pulmonary infiltration of monocyte-derived alveolar macrophages (Mo-AMs) from an aged bone marrow. These Mo-AMs displayed an enhanced profibrotic profile and a delayed transition in acquiring a homeostatic tissue-resident phenotype. This impaired Mo-AM differentiation was attributed to diminished numbers of regulatory T cells (Tregs) and the reduced availability of the anti-inflammatory cytokine IL-10 in the lung microenvironment of mice engrafted with aged bone marrow. Mechanistically, we show that Tregs are crucial providers of IL-10 that promote timely Mo-AM maturation and attenuate fibrosis progression. Our findings demonstrate the critical influence of an aged bone marrow on the development of lung fibrosis and identify a Treg-mediated resolutory axis as a potential therapeutic target for accelerated tissue repair.
2024-12-02 | GSE274253 | GEO
Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry based proteomics. In this experiment, we have compared MACS sorted BEC and full brain tissue a massive enrichment of endothelial markers including Nos3, Cdh5, and Pecam1 in BECs compared to FT.
2024-02-15 | PXD044993 | Pride