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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 1: RNA-seq)

ABSTRACT: By taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we performed an in-depth comparison of transcriptomic responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells in humanized mice promotes transcriptomic responses akin to those of human vaccinees

ORGANISM(S): Homo sapiens

PROVIDER: GSE119749 | GEO | 2018/11/28

REPOSITORIES: GEO

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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 2: scRNA-seq)

Project description:We performed an in-depth characterization and comparison of the immune system diversity and complexity in the spleen of conventional NRG-HIS mice and NFA2-HIS/Ftl3LG mice upon YFV-17D infection, a live-attenuated virus that induce that induce potent protective immunity in human. To do so, we employed Seq-Well, a recently developed platform for massively parallel single-cell RNA-Seq (scRNA-Seq), on splenocytes from NRG-HIS mice and NFA2-HIS/Flt3LG mice at six-weeks post YFV-17D infection. Our data provide an in-depth view of the cellular composition of the HIS in conventional and second-generation humanized mice. They also highlight the enhanced engraftment and functionality of the critical role of the myeloid and NK cell compartment in NFA2-HIS/Flt3LG mice, which is likely critical in promoting an enhanced transcriptomic, cellular and humoral response to YFV-17D.

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Project description:In this study, we compared the metabolic effects of TCPOBOP using lipidomic, transcriptomic, and proteomic analyzes in wild-type and humanized CAR-PXR-CYP3A4/3A7 mice. In the humanized mouse model, human CAR retains its constitutive activity in metabolism regulation; however, it is not significantly activated by TCPOBOB. TCPOBOP elevated serum and liver levels of triglycerides and promoted hepatocyte hypertrophy in humanized CAR mice. Hepatic lipidomic analysis revealed a significant accumulation of triglycerides and downregulation of its metabolites in humanized CAR mice. RNA-seq analysis has shown gene expression changes mainly involved in lipid metabolic processes and in ppar, leptine, thyroid, and circadian clock pathways. In summary, we identify TCPOBOP as a lipid metabolism disruptor in humanized CAR mice

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