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

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

PROVIDER: PRJNA490176 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7815160.fastq.gz	Fastqsanger.gz
	SRR7815170.fastq.gz	Fastqsanger.gz
	SRR7815161.fastq.gz	Fastqsanger.gz
	SRR7815171.fastq.gz	Fastqsanger.gz
	SRR7815162.fastq.gz	Fastqsanger.gz

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

Project description: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

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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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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

Project description:Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

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

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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses.

Project description:Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we provide an in-depth comparison of immune responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells promotes transcriptomic responses akin to those of human vaccinees. These enhanced transcriptomic profiles correlate with the development of an antigen-specific cellular and humoral response to YFV-17D. Altogether, our approach provides a robust scoring of the quality of the human immune response in humanized mice and highlights a rational path towards developing better pre-clinical models for studying the human immune response and disease.

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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

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