ScRNA-sequencing of non-neuron cells from hippocampus (HP) of 7 months old Mr1+/+ and Mr1-/- mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE189656 | GEO | 2022/09/28
REPOSITORIES: GEO
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Project description:scRNA-sequencing of non-neuron cells from hippocampus (HP) of 7 months old Mr1+/+ and Mr1-/- mice.
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Project description:MR1T cells are a recently discovered class of T cells that recognize antigens presented by the MHC-I–related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.
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Project description:Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Here, we assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via microarray analysis of cortical and hippocampal mRNA transcription. We used microarrays to investigate the effects of short-term (6-week) and long-term (12-week) curcumin-supplemented diet on gene expression of hippocampus and cortex in aged rats. The hippocampus and cortex of every three rats from one group were pooled together, respectively and used for RNA extraction and hybridization on Affymetrix microarrays. To ensure the reliability of the data, we conducted hybridization experiments in duplicate microarrays from each RNA sample. The tissues examined by microarray are as follows: the hippocampus and cortex of 6-week curcumin-treated 15-month-old rats, the hippocampus and cortex of 6-week no curcumin-treated 15-month-old rats (control rats), the hippocampus and cortex of 12-week curcumin-treated 15-month-old rats, the hippocampus and cortex of 12-week no curcumin-treated 15-month-old rats (control rats).
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Project description:Understanding the molecular changes associated with the aged brain forms the basis for developing potential strategies for slowing cognitive decline associated with normal aging. Focusing on the hippocampus, a critical brain region involved in learning and memory, we employed tandem mass tag methodology to investigate proteomic changes that occur in advanced aged (20-month) relative to young (3-month) C57BL/6 mice. Our analysis revealed a total of 324 proteins that were significantly altered in the old mice relative to the young mice. Upregulated proteins (236 total proteins) were enriched within several age-related processes, such as the adaptive immune response and molecular metabolic pathways, whereas downregulated proteins (88 total proteins) were mainly involved in axonogenesis and growth cone-related processes. By categorising proteins according to their cell-type enrichment in the brain, a general upregulation was observed in the level of proteins preferentially expressed in microglia, astrocytes, and oligodendrocytes. In contrast, proteins with neuron-specific expression display an overall age-related downregulation. By integrating our proteomic and transcriptomic data, we discovered a mild but significant positive correlation between mRNA and protein expression changes in the aged hippocampus. Therefore, this proteomic data is a valuable resource for age-related molecular studies.
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Project description:Mucosal-Associated Invariant T cells (MAIT cells) have a unique specificity for the microbial metabolite 5-OP-RU presented by the non-classical presentation molecule MR1. Upon activation, they release cytotoxic mediators and engage an antimicrobial activity. As a subset of T lymphocytes, MAIT development occurs in the thymus where they acquire their effector phenotype under the control of the key transcription factor ZBTB16. This particular maturation process is in contrast with conventional T cells that egress the thymus with a naive phenotype before populating the secondary lymphoid organs, and the molecular events driving the MAIT lineage decision are poorly known. In the present work, we evaluated the transcriptional events and the role of the slam-SAP pathway on the lineage decision of MR1-restricted T cells by single cell RNAseq. MAIT cells undergoing positive selection were FACS-sorted with a MR1:5-OP-RU labeled tetramer, from thymus of wild-type and sapKO mice. Their transcriptomes were captured using a 10x chromium system.
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Project description:Burkholderia sp. MR1 Genome sequencing and assembly
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