Molecular and anatomical roadmap of stroke pathology in immunodeficient mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE208605 | GEO | 2022/10/01
REPOSITORIES: GEO
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Project description:Molecular and anatomical roadmap of stroke pathology in immunodeficient mice
| PRJNA860208 | ENA
Project description:BackgroundStroke remains a leading cause of disability and death worldwide. It has become apparent that inflammation and immune mediators have a pre-dominant role in initial tissue damage and long-term recovery. Still, different immunosuppressed mouse models are necessary in stroke research e.g., to evaluate therapies using human cell grafts. Despite mounting evidence delineating the importance of inflammation in the stroke pathology, it is poorly described to what extent immune deficiency influences overall stroke outcome.MethodsHere, we assessed the stroke pathology of popular genetic immunodeficient mouse models, i.e., NOD scid gamma (NSG) and recombination activating gene 2 (Rag2-/-) mice as well as pharmacologically immunosuppressed mice and compared them to immune competent, wildtype (WT) C57BL/6J mice three weeks after injury. We performed histology, gene expression, blood serum and behavioural analysis to identify the impact of immunosuppression on stroke progression.ResultsWe detected changes in microglia activation/macrophage infiltration, scar-forming and vascular repair in immune-suppressed mice three weeks after injury. Transcriptomic analysis of stroked tissue revealed the strongest deviation from WT was observed in NSG mice affecting immunological and angiogenic pathways. Pharmacological immunosuppression resulted in the least variation in gene expression compared with the WT. These anatomical and genetic changes did not affect functional recovery in a time course of three weeks. To determine whether timing of immunosuppression is critical, we compared mice with acute and delayed pharmacological immunosuppression after stroke. Mice with delayed immunosuppression (7d) showed increased inflammatory and scarring responses compared to animals acutely treated with tacrolimus, thus more closely resembling WT pathology. Transplantation of human cells in the brains of immunosuppressed mice led to prolonged cell survival in all immunosuppressed mouse models, which was most consistent in NSG and Rag2-/- mice.ConclusionsWe detected distinct anatomical and molecular changes in the stroke pathology between individual immunosuppressed mouse models that should be considered when selecting an appropriate mouse model for stroke research.
| S-EPMC9785704 | biostudies-literature
Project description:Methionine, a sulfur-containing essential amino acid, is a key component of dietary proteins important for protein synthesis, sulfur metabolism, antioxidant defense, and signaling. However, the role of methionine in cancer progression remains inconclusive. On one hand, dietary methionine restriction is known to repress cancer growth and improve cancer therapy in xenografted tumors. On the other hand, methionine is also critical for T cell activation and differentiation, making it a potential tumor suppression nutrient by enhancing T cell-mediated anti-tumor immunity. Here we investigated the interaction between dietary methionine, immune cells, and cancer cells by allografting CT26.WT mouse colon carcinoma cells into immunocompetent Balb/c mice or immunodeficient NSG mice, then analyzed how dietary methionine contents affect their growth. Our results show that dietary methionine restriction suppresses tumor growth in immunodeficient NSG mice but promotes tumor progression in immunocompetentt Balb/c mice.
2023-06-14 | GSE165993 | GEO
Project description:Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells developed blood M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Singe cell RNAseq analyses showed non-malignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma-engrafted mice given CAR T-cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results establish that NSG+hIL6 mice provide an effective patient derived xenograft model for study and preclinincal drug development for myeloma and related plasma cell disorders.
2024-10-14 | GSE246140 | GEO
Project description:Purpose: Understanding the role of an active immunesystem in ageing. Methods: Male NSG (NOD scid gamma) immunodeficient mice were maintained in normal housing condition. Islet cells were isolated at different age points and mRNA were extracted before shipping to Qiagen for analysis. Results: In NSG mice multiple of the metabolic pathways that are observed to be deregulated in ageing immunocompotent mice are infered to be sustained.
2025-04-03 | GSE231710 | GEO
Project description:Three groups of sex- and aged-matched 9-12 week old C57BL/6 wild type mice and gp91-/-phox mice were infected by i.v. injection of bacterial suspensions: Group 1 represents wild type C57BL/6 mice infected with virulent S. Typhimurium SL1344 grown in vitro. (Raw files: OTNCS_AGSL1344#3C#9C#10C-XX) Group 2 represents wild type C57BL/6 mice infected with virulent S. Typhimurium SL1344 grown in vivo for 72 h in the Group 1 C57BL/6 mice. (Raw files: OTNCS_AGSL1344#9F#10F-XX) Group 3 represents immunodeficient gp91-/-phox mice infected with virulent S. Typhimurium SL1344 grown in vitro. (Raw files: OTNCS_AGSL1344#11C#12C#13C-XX) And Input (Raw files: OTNCS_AGSL1344mixedAa-XX and OTNCS_AGSL1344mixedAb-XX)
2018-10-26 | PXD005855 | Pride
Project description:The relative importance of T/B lymphocytes and NK cells during acute myeloid leukemia (AML) progression has been unclear. In this study, we compared gene expression profiles of mouse AML cells expressing MLL-AF9 collected from immunologically normal wild-type (WT) C57BL/6 mice, Rag2-/- mice lacking mature T and B cells, and NSG mice lacking T, B and NK cells.
2023-12-27 | GSE245359 | GEO
Project description:Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis of various developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches.
2017-06-16 | GSE100077 | GEO
Project description:Immunotherapeutic strategies are increasingly important in neuro-oncology and the elucidation of escape mechanisms which lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing wildtype and PD-1-/- mice survived significantly longer than immunodeficient Pfp/Rag2-/- mice. While tumors in Pfp/Rag2-/- mice were highly polyclonal, immunoedited tumors in WT and PD-1-/- mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in wildtype mice were distinguished by an interferon-gamma-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even stronger to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, cancer immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas.
2020-08-31 | GSE151284 | GEO
Project description:Immunotherapeutic strategies are increasingly important in neuro-oncology and the elucidation of escape mechanisms which lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing wildtype and PD-1-/- mice survived significantly longer than immunodeficient Pfp/Rag2-/- mice. While tumors in Pfp/Rag2-/- mice were highly polyclonal, immunoedited tumors in WT and PD-1-/- mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in wildtype mice were distinguished by an interferon-gamma-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even stronger to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, cancer immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas.
2020-08-31 | GSE151283 | GEO