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Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Mouse Single Cell Dataset]

ABSTRACT: Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Mouse Single Cell Dataset]

PROVIDER: PRJNA1098410 | ENA |

REPOSITORIES: ENA

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	SRR28604504.fastq.gz	Fastqsanger.gz

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Barcoded viral tracing identifies bi-directional immunosuppressive astrocyte-glioblastoma cross-talk

Project description:Barcoded viral tracing identifies bi-directional immunosuppressive astrocyte-glioblastoma cross-talk

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Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Human Single Cell Dataset]

Project description:Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Human Single Cell Dataset]

| PRJNA1098411 | ENA

Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Mouse Single Cell Dataset]

Project description:Glioblastoma (GBM) is the most lethal primary brain malignancy. Immunosuppression in the GBM tumor microenvironment (TME) presents a major barrier to immune-targeted therapies. However, our understanding of mechanisms of immunomodulation in the GBM TME is still limited. To address this challenge, we developed a viral barcode interaction tracing approach for the analysis of cell-cell communication in the TME in GBM samples and preclinical models with single-cell resolution, which we combined with single-cell and bulk RNA-seq analyses of GBM clinical samples and pre-clinical models, human organotypic GBM slice cultures, in vivocell-specific CRISPR/Cas9-driven genetic perturbations and human and mousein vitroexperimental systems to identify a novel bi-directional communication pathway between ANXA1 expressed inastrocytes and its receptor FPR1 expressed by GBM cells that limits anti-tumor immune responses. ANXA1 expression in astrocytes and FPR1 expression in cancer cells are associated with shorter survival and earlier recurrence in GBM patients. The inactivation of astrocyte-glioma ANXA1/FPR1-signaling enhanced tumor specific CD4+ and CD8+ T-cell responses, increasing tumor infiltration by neoantigen-specific CD8+ T cells while limiting transcriptional modules linked to T-cell exhaustion; ANXA1/FPR1-signaling inactivation also boosted tumor-associated macrophage responses. Using pre-clinical models and human GBMin vitroexperimental systems, we established that FPR1 inhibits immunogenic necroptosis in tumor cells, while ANXA1 retrograde signaling suppresses NF-kB and inflammasome activation within astrocytes. In summary, we developed a new barcoding approach to analyze TME cell-cell interactions with single-cell resolution in clinical samples and pre-clinical models, and used it to identify a novel pathway of bidirectional ANXA1–FPR1 astrocyte-GBM communication which promotes immunoevasion and cancer progression.

2025-04-28 | GSE263613 | GEO

Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Human Single Cell Dataset]

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Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Mouse Bulk RNA-Seq Dataset of Monocytes, T Cells and Astrocytes 5OLJ]

Project description:Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Mouse Bulk RNA-Seq Dataset of Monocytes, T Cells and Astrocytes 5OLJ]

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Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Mouse Bulk RNA-Seq Dataset of Monocytes, T Cells and Astrocytes 63FG]

| PRJNA1099133 | ENA

Barcoded viral tracing identifies bi-directional immunosuppressive astrocyte-glioblastoma cross-talk

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-04-30 | GSE286996 | GEO

Bi-directional immunosuppressive interactions between astrocytes and glioblastoma cells identified by barcoded viral tracing [Mouse Bulk RNA-Seq Dataset of Monocytes, T Cells and Astrocytes 63FG]

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Translation of bi-directional transcripts generates peptides for the MHC-I pathway.

Project description:Antisense transcripts play an important role in generating regulatory non-coding RNAs but if these transcripts are also translated and for what purpose is yet poorly understood. Isolation of polysome fractions followed by RNA sequencing and mass spectrometry analysis of a six frame data-base revealed nascent peptides originating from different reading frames of bi-directional transcripts. Two peptides originating from the antisense strand stimulated the proliferation of CD8+ T cells when presented to peripheral blood mononuclear cells (PBMCs) from nine healthy donors. An antigenic peptide derived from the reverse strand of two cDNA constructs was presented on MHC-I molecules and induced CD8+ T cell activation. These results demonstrate that three frame translation of bi-directional transcripts generate antigenic peptide substrates for the immune system. This discovery holds significance for better understanding the origin of self-discriminating peptide substrates for the MHC-I pathway and for enhancing immune-based therapies against infected or transformed cells.

2025-05-07 | PXD057573 | Pride

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