Hypoxic stress dysregulates functions of glioma-associated myeloid cells through epigenomic and transcriptional programs
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PROVIDER: PRJNA1280097 | ENA |
REPOSITORIES: ENA
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Project description:Hypoxic stress dysregulates functions of glioma-associated myeloid cells through epigenomic and transcriptional programs [CUT&RUN]
| PRJNA1280101 | ENA
Project description:Hypoxic stress dysregulates functions of glioma-associated myeloid cells through epigenomic and transcriptional programs [ATAC-seq]
| PRJNA1173214 | ENA
Project description:Hypoxic stress dysregulates functions of glioma-associated myeloid cells through epigenomic and transcriptional programs [RNA-seq]
| PRJNA1173213 | ENA
Project description:Hypoxia rapidly alters gene expression to allow cellular adaptation to challenging conditions and support tumour growth. Hypoxia also affects the chromatin structure by modifications of histones and DNA methylation. Glioblastoma (GBM) is an aggressive, deadly primary brain tumour for which there is no effective treatment. The tumour microenvironment of GBM is highly heterogeneous, with infiltration of glioma-associated microglia and macrophages (GAMs) and the presence of necrotic, hypoxic regions. The mechanisms through which hypoxia alters the tumour microenvironment and regulates functions of infiltrating immune cells remain poorly understood. Here, we show that hypoxia modulates the expression of myeloid markers in distinct ways: upregulates the monocytic marker Lgals3 expression and downregulates the microglial markers P2ry12 and Tmem119 in microglial and monocytic GAMs in vitro and in vivo, as shown using human and mouse GBM single-cell transcriptomics datasets. The genome-wide hypoxia-dependent transcriptomic changes in microglial cells were determined in microglia-glioma co-cultures. Numerous GAM subtype markers were dysregulated in response to hypoxic stress due to associated changes in chromatin accessibility, as determined using ATACseq. While hypoxia alone drives a decrease of the overall chromatin accessibility at gene promoters, the exposure to glioma cells under hypoxic conditions leads to both increases and decreases of chromatin accessibility at promoter regions in microglial cells. Hypoxia downregulates the chromatin accessibility at the regions enriched in motifs of transcription factors regarded as master regulators of microglial cell identity and function, including SPI1 or IRF8. Moreover, changes in histone acetylation are responsible for Lgals3 upregulation and lipid accumulation in GAMs in hypoxic conditions. Overall, our data highlights the importance of hypoxic stress as a strong intratumoral regulator of myeloid cell functions, which adds complexity to the characterisation of particular GAMs subpopulations.
2025-08-28 | GSE300328 | GEO
Project description:Hypoxia rapidly alters gene expression to allow cellular adaptation to challenging conditions and support tumour growth. Hypoxia also affects the chromatin structure by modifications of histones and DNA methylation. Glioblastoma (GBM) is an aggressive, deadly primary brain tumour for which there is no effective treatment. The tumour microenvironment of GBM is highly heterogeneous, with infiltration of glioma-associated microglia and macrophages (GAMs) and the presence of necrotic, hypoxic regions. The mechanisms through which hypoxia alters the tumour microenvironment and regulates functions of infiltrating immune cells remain poorly understood. Here, we show that hypoxia modulates the expression of myeloid markers in distinct ways: upregulates the monocytic marker Lgals3 expression and downregulates the microglial markers P2ry12 and Tmem119 in microglial and monocytic GAMs in vitro and in vivo, as shown using human and mouse GBM single-cell transcriptomics datasets. The genome-wide hypoxia-dependent transcriptomic changes in microglial cells were determined in microglia-glioma co-cultures. Numerous GAM subtype markers were dysregulated in response to hypoxic stress due to associated changes in chromatin accessibility, as determined using ATACseq. While hypoxia alone drives a decrease of the overall chromatin accessibility at gene promoters, the exposure to glioma cells under hypoxic conditions leads to both increases and decreases of chromatin accessibility at promoter regions in microglial cells. Hypoxia downregulates the chromatin accessibility at the regions enriched in motifs of transcription factors regarded as master regulators of microglial cell identity and function, including SPI1 or IRF8. Overall, our data highlights the importance of hypoxic stress as a strong intratumoral regulator of myeloid cell functions, which adds complexity to the characterisation of particular GAMs subpopulations.
2025-08-28 | GSE279538 | GEO
Project description:Hypoxia rapidly alters gene expression to allow cellular adaptation to challenging conditions and support tumour growth. Hypoxia also affects the chromatin structure by modifications of histones and DNA methylation. Glioblastoma (GBM) is an aggressive, deadly primary brain tumour for which there is no effective treatment. The tumour microenvironment of GBM is highly heterogeneous, with infiltration of glioma-associated microglia and macrophages (GAMs) and the presence of necrotic, hypoxic regions. The mechanisms through which hypoxia alters the tumour microenvironment and regulates functions of infiltrating immune cells remain poorly understood. Here, we show that hypoxia modulates the expression of myeloid markers in distinct ways: upregulates the monocytic marker Lgals3 expression and downregulates the microglial markers P2ry12 and Tmem119 in microglial and monocytic GAMs in vitro and in vivo, as shown using human and mouse GBM single-cell transcriptomics datasets. The genome-wide hypoxia-dependent transcriptomic changes in microglial cells were determined in microglia-glioma co-cultures. Numerous GAM subtype markers were dysregulated in response to hypoxic stress due to associated changes in chromatin accessibility, as determined using ATACseq. While hypoxia alone drives a decrease of the overall chromatin accessibility at gene promoters, the exposure to glioma cells under hypoxic conditions leads to both increases and decreases of chromatin accessibility at promoter regions in microglial cells. Hypoxia downregulates the chromatin accessibility at the regions enriched in motifs of transcription factors regarded as master regulators of microglial cell identity and function, including SPI1 or IRF8. Overall, our data highlights the importance of hypoxic stress as a strong intratumoral regulator of myeloid cell functions, which adds complexity to the characterisation of particular GAMs subpopulations.
2025-08-28 | GSE279536 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-08-28 | GSE300330 | GEO
Project description:The tumor microenvironment (TME) of gliomas comprises glioma cells and surrounding cells, such as astrocytes, macrophages, T cells, and neurons. In the TME, glioma cells can activate normal human astrocytes (NHAs) through the secretion of exosomes and the activation of astrocytes can further improve the progression of glioma, leading to a poor prognosis for patients. However, the molecular mechanisms underlying NHAs activation by gliomas remain largely unknown. It this study, glioma-derived exosomes (GDEs) play an important role in the modulation of autophagy and activation of NHAs. Compared with normoxic glioma-derived exosomes, hypoxic glioma-derived exosomes (H-GDEs) further improved autophagy and activation of astrocytes, which strongly promoted the progression of glioma cells. In an miRNA array between two types of exosomes from gliomas, miR-423-3p was highly expressed in H-GDEs and played an important role in autophagy, resulting in the activation of NHAs. The mechanism by which hypoxic glioma cells react with NHAs to create an immunosuppressive microenvironment was identified and 15d-PGJ2 was established as an effective inhibitor of miR-423-3p to suppress NHA activation. These findings provide new insights into the diagnosis and treatment of gliomas by targeting autophagy and miR-423-3p expression.
2025-01-17 | GSE286468 | GEO
Project description:Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations, however the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG, and association with the Rela oncofusion in EPN. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis.
2022-07-13 | PXD033863 | Pride
Project description:Under hypoxic conditions, nitroimidazole compounds accumulate in cells in their reduced form and have oxygen-mimetic effects, serving as markers of hypoxia and radiosensitizers. The full potential of their bioreductive metabolism, including cytotoxicity for cancer stem cells, has not been sufficiently explored, however. Here we investigated the changes in gene expression induced by treatment with 2-nitroimidazole doranidazole in murine glioma stem cells, under normoxic or hypoxic conditions.
2020-08-18 | GSE135858 | GEO