Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Homo sapiens

ABSTRACT: APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer's Disease Phenotypes in Human iPSC-Derived Brain Cell Types

PROVIDER: PRJNA399530 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR5956450.fastq.gz	Fastqsanger.gz
	SRR5956460_1.fastq.gz	Fastqsanger.gz
	SRR5956460_2.fastq.gz	Fastqsanger.gz
	SRR5956470.fastq.gz	Fastqsanger.gz
	SRR5956451.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 34

Similar Datasets

Cholesterol and matrisome pathways dysregulated in APOE ε4 human microglia and astrocytes [populationAPOE]

Project description:The impact of Apolipoprotein E4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on human brain cellular function remains unclear. Here we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cell models, post-mortem brain and APOE targeted replacement mice. Population and isogenic models uncover that APOE4 local haplotype rather than a single risk allele alone contributes to the risk. Global transcriptomic analyses reveal human specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia. APOE4 leads to elevated de novo cholesterol synthesis despite the intracellular cholesterol accumulation due to lysosomal sequestration of cholesterol in astrocytes. Transcriptome analyses uncovered Matrisome dysregulation associated with upregulated chemotaxis, glial activation and lipid biosynthesis in astrocytes, co-cultured with neurons that recapitulates altered astrocyte matrisome signaling in human brain. Thus, APOE4 initiates glia-specific cell and non-cell autonomous dysregulation that may contribute to increased AD risk.

2022-06-23 | GSE190187 | GEO

Cholesterol and matrisome pathways dysregulated in APOE ε4 human microglia and astrocytes [mouseApoe]

2022-06-23 | GSE190186 | GEO

Cholesterol and matrisome pathways dysregulated in APOE ε4 human microglia and astrocytes [isogenicAPOE]

2022-06-23 | GSE190185 | GEO

APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer's Disease Phenotypes in Human iPSC-Derived Brain Cell Types

Project description:The apolipoprotein E4 (APOE4) variant is the single greatest genetic risk factor for sporadic Alzheimer's disease (sAD). However, the cell-type-specific functions of APOE4 in relation to AD pathology remain understudied. Here, we utilize CRISPR/Cas9 and induced pluripotent stem cells (iPSCs) to examine APOE4 effects on human brain cell types. Transcriptional profiling identified hundreds of differentially expressed genes in each cell type, with the most affected involving synaptic function (neurons), lipid metabolism (astrocytes), and immune response (microglia-like cells). APOE4 neurons exhibited increased synapse number and elevated Ab42 secretion relative to isogenic APOE3 cells while APOE4 astrocytes displayed impaired Ab uptake and cholesterol accumulation. Notably, APOE4 microglia-like cells exhibited altered morphologies, which correlated with reduced Ab phagocytosis. Consistently, converting APOE4 to APOE3 in brain cell types from sAD iPSCs was sufficient to attenuate multiple AD-related pathologies. Our study establishes a reference for human cell-type-specific changes associated with the APOE4 variant.

2018-05-31 | GSE102956 | GEO

Comparaison of APOE4 and APOE3 transcriptomic profiles from derived cell lines in absence or presence of an inflammatory stimulus

Project description:Our objective was to study some of the molecular changes that associate with APOE4, ultimately aiming at identifying new mechanisms that support exacerbated neuroinflammation as a cause of functional deterioration in Alzheimer's disease (AD). We hypothesize that the increased risk of developing AD in APOE4 carriers could be the consequence of altered inflammatory regulatory functions in astrocytes, which would be key effectors of the pathological process.

2021-02-01 | E-MTAB-9625 | biostudies-arrayexpress

E-MTAB-8802

Project description:RNA sequencing of human iPSC-derived brain microvascular endothelial cells.

2025-01-16 | E-MTAB-8802 | ExpressionAtlas

E-GEOD-66354

Project description:Gene expression profile of pediatric and adult brain tumor types and normal brain

2025-01-24 | E-GEOD-66354 | ExpressionAtlas

APOE determines cell type-specific pathological landscape of Alzheimer's disease

Project description:The apolipoprotein E (APOE) gene is the strongest genetic risk modifier for Alzheimer's disease (AD), with the APOE4 allele increasing risk and APOE2 decreasing it compared to the common APOE3 allele. Using single-nuclei RNA sequencing of the temporal cortex from APOE2 carriers, APOE3 homozygotes, and APOE4 carriers, we found that AD-associated transcriptomic changes were highly APOE genotype-dependent. Comparing AD with controls, APOE2 carriers showed upregulated synaptic and myelination-related pathways, preserving synapses and myelination at the protein level. Conversely, these pathways were downregulated in APOE3 homozygotes, resulting in reduced synaptic and myelination proteins. In APOE4 carriers, excitatory neurons displayed reduced synaptic pathways similar to APOE3, but oligodendrocytes showed upregulated myelination pathways like APOE2. However, their synaptic and myelination protein levels remained unchanged or increased. APOE4 carriers also showed increased pro-inflammatory signatures in microglia but reduced responses to amyloid-β pathology. These findings reveal APOE genotype-specific molecular alterations in AD across cell types.

2025-03-17 | GSE237718 | GEO

E-PROT-31

Project description:Proteomic Atlas of the human brain in Alzheimer's disease

2021-05-25 | E-PROT-31 | ExpressionAtlas

E-PROT-61

Project description:Proteomic Atlas of the Human Brain in Alzheimer's Disease

2021-05-25 | E-PROT-61 | ExpressionAtlas