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Xenotransplantation of Human PSC-derived Microglia Creates a Chimeric Mouse Brain Model that Recapitulates Features of Adult Human Microglia

ABSTRACT: Xenotransplantation of Human PSC-derived Microglia Creates a Chimeric Mouse Brain Model that Recapitulates Features of Adult Human Microglia

PROVIDER: PRJNA530391 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8835866_1.fastq.gz	Fastqsanger.gz
	SRR8835866_2.fastq.gz	Fastqsanger.gz
	SRR8835867_1.fastq.gz	Fastqsanger.gz
	SRR8835867_2.fastq.gz	Fastqsanger.gz
	SRR8835868_1.fastq.gz	Fastqsanger.gz

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Xenotransplantation of Human PSC-derived Microglia Creates a Chimeric Mouse Brain Model that Recapitulates Features of Adult Human Microglia

Project description:Microglia, the brain-resident macrophages, exhibit highly dynamic functions in neurodevelopment and neurodegeneration. Human microglia possess unique features as compared to mouse microglia, but our understanding of human microglial functions is largely limited by an inability to obtain human microglia under resting, homeostatic states. We developed a human pluripotent stem cell (hPSC)-based microglial chimeric mouse brain model by transplanting hPSC-derived primitive macrophage precursors into neonatal mouse brains. The engrafted human microglia widely disperse in the brain and replace mouse microglia in corpus callosum at 6 months post-transplantation. Single-cell RNA-sequencing of the hPSC microglial chimeric mouse brains reveals that xenografted hPSC-derived microglia largely retain human microglial identity, as they exhibit signature gene expression patterns consistent with physiological human microglia and recapitulate heterogeneity of adult human microglia. Importantly, the chimeric mouse brain also models species-specific transcriptomic differences in the expression of neurological disease-risk genes in microglia. This model will serve as a novel tool to study the role of human microglia in brain development and degeneration.

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The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia in a xenotransplantation model of Alzheimer’s disease [RNA-seq]

Project description:Microglia play a key role in the response to amyloid beta in Alzheimer’s disease (AD). In this context, the major transcriptional response of microglia is the upregulation of APOE, the strongest late-onset AD risk gene. Of its three isoforms, APOE2 is thought to be protective, while APOE4 increases AD risk. We hypothesised that the isoforms functionally alter microglia by shaping their transcriptomic and chromatin landscapes. We used RNA- and ATAC-sequencing to profile gene expression and chromatin accessibility of human microglia isolated from a xenotransplantation model of AD. We identified widespread transcriptomic and epigenomic differences which are dependent on APOE genotype, and are corroborated across the profiling assays.

2024-07-08 | GSE271385 | GEO

The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia in a xenotransplantation model of Alzheimer’s disease [ATAC-seq]

Project description:Microglia play a key role in the response to amyloid beta in Alzheimer’s disease (AD). In this context, the major transcriptional response of microglia is the upregulation of APOE, the strongest late-onset AD risk gene. Of its three isoforms, APOE2 is thought to be protective, while APOE4 increases AD risk. We hypothesised that the isoforms functionally alter microglia by shaping their transcriptomic and chromatin landscapes. We used ATAC- and ATAC-sequencing to profile gene expression and chromatin accessibility of human microglia isolated from a xenotransplantation model of AD. We identified widespread transcriptomic and epigenomic differences which are dependent on APOE genotype, and are corroborated across the profiling assays.

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PSC-IBD mucosal biology

Project description:Comparative colonic mucosal transcriptomics of 10 patients with PSC-IBD, 10 UC and 10 Healthy controls

2019-09-01 | E-MTAB-7915 | biostudies-arrayexpress

PSC-IBD mucosal biology

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