Cross-Species Transcriptomic Integration Reveals a Conserved, MIRO1-Mediated Macrophage-to-T Cell Signaling Axis Driving Immunosuppression in Glioma
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE324505 | GEO | 2026/03/12
REPOSITORIES: GEO
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Project description:We generated bulk RNA sequencing (RNA-seq) data from human glioma surgical resections treated ex vivo with a MIRO1-binding compound (MR3) or vehicle control. Fresh tumor specimens were processed and cultured under controlled conditions prior to RNA extraction and high-throughput transcriptomic profiling to characterize treatment-associated gene expression changes within the tumor microenvironment (TME). The dataset captures global transcriptional programs from tumor tissue, reflecting contributions from malignant cells as well as stromal and immune components present in the resections. These data enable analysis of MIRO1-dependent transcriptional regulation in human glioma and facilitate cross-species integration with murine single-nucleus RNA-seq datasets. This resource supports investigation of mitochondrial-associated transcriptional programs and their impact on immune microenvironment remodeling in human glioma.
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Project description:We generated single-nucleus RNA sequencing (snRNA-seq) data from murine gliomas treated in vivo with a MIRO1-binding compound or vehicle control. Tumors were dissociated and processed for nucleus isolation followed by high-throughput transcriptomic profiling to characterize cell-type-specific gene expression programs within the tumor microenvironment (TME). The dataset captures malignant cells and diverse stromal and immune populations, including macrophages, microglia, and T cells, enabling analysis of treatment-associated transcriptional changes at single-cell resolution. These data provide a resource for investigating mitochondrial-associated transcriptional regulation and immune microenvironment remodeling in murine glioma.
2026-03-12 | GSE324504 | GEO
Project description:Cross-Species Transcriptomic Integration Reveals a Conserved, MIRO1-Mediated Macrophage-to-T Cell Signaling Axis Driving Immunosuppression in Glioma
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Project description:Glioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic patterns across four mammalian hosts: rats, mice, dogs, and humans. Given the inherent intra-tumoral molecular heterogeneity of human glioma, we focused this study on tumors with upregulation of the platelet-derived growth factor signaling axis, a common and early alteration in human gliomagenesis. The results reveal core neoplastic alterations in mammalian glioma, as well as unique contributions of the tumor host to neoplastic processes. Notable differences were observed in gene expression patterns as well as related biological pathways and cell populations known to mediate key elements of glioma biology, including angiogenesis, immune evasion, and brain invasion. These data provide new insights regarding mammalian models of human glioma, and how these insights and models relate to our current understanding of the human disease.
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Project description:Despite maximal therapy, malignant gliomas have a very poor prognosis. Patients with glioma express significant immune defects, including CD4 lymphopenia, increased fractions of regulatory T cells in peripheral blood and shifts in cytokine profiles from Th1 to Th2. Recent studies have focused on ways to combat immunosuppression in patients with glioma as well as in animal models for glioma. We concentrate on two specific ways to combat immunosuppression: inhibition of TGF-beta signaling and modulation of regulatory T cells. TGF-beta signaling can be interrupted by antisense oligonucleotide technology, TGF-beta receptor I kinase inhibitors, soluble TGF-beta receptors and antibodies against TGF-beta. Regulatory T cells have been targeted with antibodies against T-cell markers, such as CD25, CTLA-4 and GITR. In addition, vaccination against Foxp3 has been explored. The results of these studies have been encouraging; combating immunosuppression may be one key to improving prognosis in malignant glioma.
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Project description:BackgroundCauliflower mosaic virus (CaMV) and Rice tungro bacilliform virus (RTBV) belong to distinct genera of pararetroviruses infecting dicot and monocot plants, respectively. In both viruses, polycistronic translation of pregenomic (pg) RNA is initiated by shunting ribosomes that bypass a large region of the pgRNA leader with several short (s)ORFs and a stable stem-loop structure. The shunt requires translation of a 5'-proximal sORF terminating near the stem. In CaMV, mutations knocking out this sORF nearly abolish shunting and virus viability.Methodology/principal findingsHere we show that two distant regions of the CaMV leader that form a minimal shunt configuration comprising the sORF, a bottom part of the stem, and a shunt landing sequence can be replaced by heterologous sequences that form a structurally similar configuration in RTBV without any dramatic effect on shunt-mediated translation and CaMV infectivity. The CaMV-RTBV chimeric leader sequence was largely stable over five viral passages in turnip plants: a few alterations that did eventually occur in the virus progenies are indicative of fine tuning of the chimeric sequence during adaptation to a new host.Conclusions/significanceOur findings demonstrate cross-species functionality of pararetroviral cis-elements driving ribosome shunting and evolutionary conservation of the shunt mechanism. We are grateful to Matthias Müller and Sandra Pauli for technical assistance. This work was initiated at Friedrich Miescher Institute (Basel, Switzerland). We thank Prof. Thomas Boller for hosting the group at the Institute of Botany.
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