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ScRNA-sequencing of non-neuron cells from hippocampus (HP) of 7 months old Mr1+/+ and Mr1-/- mice.

ABSTRACT: scRNA-sequencing of non-neuron cells from hippocampus (HP) of 7 months old Mr1+/+ and Mr1-/- mice.

PROVIDER: PRJNA784091 | ENA |

REPOSITORIES: ENA

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scRNA-sequencing of non-neuron cells from hippocampus (HP) of 7 months old Mr1+/+ and Mr1-/- mice.

Project description:The purpose of this experiment is to examine the cellular and molecular changes in the microglia and other non-neuron cells in the hippocampus of 7 month old Mr1+/+ and Mr1-/- mice.

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Project description:Mr1 knockout (Mr1−/−) mice, in which thymic cells lose the ability to promote the development of mature Mucosal-associated invariant T (MAIT) cells, induced systemic MAIT cell depletion. MAIT cells often exhibit altered functions during fibrosis and inflammatory diseases. Here we used intraperitoneal injections of 4.25% PD fluid (0.1 mL/g) daily for six weeks to mimic peritoneal dialysis (PD) related fibrosis in mice, and investigated whether Mr1 knockout could ameliorated PD-induced changes in peritoneal transcriptome. We analyzed bulk RNA-seq of peritoneums from Mr1+/+ + PBS group (n=3), Mr1+/+ + PD group (n=3), Mr1-/- + PBS group (n=2), and Mr1-/- + PD group (n=2), and demonstrated that Mr1 knockout could ameliorated PD-induced activation in fibrosis, hyperglycolysis, and mTORC1 signalings. In addition, the activation scores of these pathways are positively correlated with each other.

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snRNA-seq of the hippocampus of Mr1+/+ P301S mice and Mr1-/- P301S mice

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Project description:MHC class I-related molecule MR1 presents riboflavin-derived microbial metabolites and folate-derivatives to mucosal-associated invariant T cells, but it is unknown whether MR1 can bind alternative antigens that stimulate other T cell lineages. Here we report that human T cells displaying diverse TCR-α and β chains recognize MR1-expressing cells in the absence of microbial ligands and respond to recombinant MR1 molecules loaded with antigens extracted from stimulatory targets. Transcriptome analysis revealed functional heterogeneity of MR1-reactive T cells (MR1T cells), which displayed differential expression of various transcription factors regulating T cell polarization, proliferation and apoptosis. Accordingly, MR1T cells displayed multiple profiles of chemokine receptor expression and secreted variable combinations of cytokines and growth factors, suggesting a diversity of immunological roles across numerous tissues. Functionally, MR1T cells were capable of inducing dendritic cell maturation and stimulating anti-microbial responses in intestinal epithelial cells. These data demonstrate that MR1 presents endogenous antigens to a novel population of functionally diverse human T cells.

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Macrophages are specialised at MR1 antigen presentation to MAIT cells [RNA-seq]

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Macrophages are specialised at MR1 antigen presentation to MAIT cells [ATAC-seq]

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Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells

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