Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic study of human brain organoids in Alzheimer's Disease

ABSTRACT: Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by the presence ofamyloid beta plaque deposition, tau hyperphosphorylation and decline in cognition. Mechanistically, these proteostatic changes are able to induce mitochondrial calcium overload that could lead to cell death. Conventional preclinical 2D in vitro AD models do not accurately recapitulate these hallmarks. As an effort to improve AD modeling, we have established iPSC-derived brain organoids (BO) harboring the PSEN1 Delta-E9 mutation and compared them to their CRISPR-Cas9-corrected isogenic controls. Organoids were also treated with an BACE-1 Inhibitor. As an effort to build into the complexity of organoid modeling, we co-cultured these organoids with their congenic iPSC-derived microglia-like cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266358 | GEO | 2024/11/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Modeling sporadic Alzheimer’s disease in human brain organoids under serum exposure

Project description:Although sporadic AD (sAD) accounts for the majority of AD cases, the underlying mechanisms remain largely unknown. Here we modeled sAD using human induced pluripotent stem cell (iPSC)-derived three-dimensional brain organoids. We exposed brain organoids to serum to mimic the serum exposure consequence of BBB breakdown in AD patient brains. The serum-exposed brain organoids were able to recapitulate AD-like pathologies, including increased Aβ aggregates and p-Tau level, synaptic loss, and impaired calcium signaling and neural network. Serum exposure increased Aβ and p-Tau levels through inducing BACE and GSK3α/β levels, respectively. In addition, single-cell transcriptomic analysis of brain organoids revealed that serum exposure reduced synaptic function in both neurons and astrocytes, and induced immune response in astrocytes. The human brain organoid-based sAD model established in this study could provide a powerful platform for both mechanistic study and therapeutic development.

2021-09-29 | GSE164089 | GEO

Human induced pluripotent stem cells derived from a sporadic Alzheimer's disease patient

Project description:Induced pluripotent stem cell (iPSC) disease models have been generated for a number of diseases, and some have shown their potential utilization for pathological and drug toxicological evaluations. We have generated two hiPSC clones from a non-familial Alzheimerâs patient (AD-iPSCs), which expressed typical undifferentiated markers and fulfilled standard pluripotency assays. Genome-wide microarray analysis revealed that AD-iPSCs are highly similar to control hiPSCs and hESCs, albeit with some noticeable differences in several genes: DNAJC15, GRPR, NAIP and SNORD116-18. Several other biomarkers were differentially expressed in AD-iPSC clones, which were implicated in memory impairment and AD. Furthermore, well characterized familial AD-associated genes (APP, PSEN1, PSEN2) and non-familial (A2M, APOE, GAP43, MAOA, MPO, PLAT, PLAU, SORL1, SNCA) exhibited different expression patterns but were largely reset upon reprogramming into a pluripotent state. Overall, hiPSCs can be good candidates for AD modeling and may represent an in vitro alternative to studying disease mechanisms and drug discovery/toxicology studies. Fibroblasts and two hiPSC clones from a non-familial Alzheimerâs patient (AD-iPSCs) were analyzed. For each cell sample, 2-3 biological replicates were obtained.

2015-12-31 | E-GEOD-31163 | biostudies-arrayexpress

Gene expression analysis of astrocytes differentiated from iPS cells generated from the fibroblasts of PSEN1deltaE9 mutant AD and their isogenic control iPS lines

Project description:Mutations in presenilin 1 (PSEN1) cause a familiar form of Alzheimer's disease (AD). We have obtained skin biopsies from two individuals carrying PSEN1 exon9 deletion and reprogrammed skin fibroblasts into induced pluripotent stem cells (iPSCs). To get controls, we have corrected PSEN1 exon9 deletion by CRISPR/Cas9 technique. Since astrocytes play role in AD pathogenesis, we further differentiated iPSCs into astrocytes. We ran RNA sequencing analysis to compare our iPSC-derived astrocytes with previously published data on human astrocytes and to identify genes and pathways affected by PSEN1 exon 9 deletion.

2019-12-31 | GSE138695 | GEO

Human induced pluripotent stem cells derived from a sporadic Alzheimer's disease patient

Project description:Induced pluripotent stem cell (iPSC) disease models have been generated for a number of diseases, and some have shown their potential utilization for pathological and drug toxicological evaluations. We have generated two hiPSC clones from a non-familial Alzheimer’s patient (AD-iPSCs), which expressed typical undifferentiated markers and fulfilled standard pluripotency assays. Genome-wide microarray analysis revealed that AD-iPSCs are highly similar to control hiPSCs and hESCs, albeit with some noticeable differences in several genes: DNAJC15, GRPR, NAIP and SNORD116-18. Several other biomarkers were differentially expressed in AD-iPSC clones, which were implicated in memory impairment and AD. Furthermore, well characterized familial AD-associated genes (APP, PSEN1, PSEN2) and non-familial (A2M, APOE, GAP43, MAOA, MPO, PLAT, PLAU, SORL1, SNCA) exhibited different expression patterns but were largely reset upon reprogramming into a pluripotent state. Overall, hiPSCs can be good candidates for AD modeling and may represent an in vitro alternative to studying disease mechanisms and drug discovery/toxicology studies.

2015-12-31 | GSE31163 | GEO

Benchmarking brain organoid recapitulation of fetal corticogenesis

Project description:Brain organoids (BO) enabled the investigation of human corticogenesis in-vitro with an increasing range of protocols achieving its remarkable recapitulation. However, we lack a resource gathering fetal cortex-specific gene co-expression patterns and their behavior in BO. We complement the current knowledge with a benchmarking of BO versus human corticogenesis, integrating: transcriptomes from in-house differentiated cortical BO (CBO), in-house processed human fetal brain samples, analysis of transcriptomes from different BO systems and of pre-natal cortical samples from the BrainSpan Atlas.

2022-12-31 | E-MTAB-11239 | biostudies-arrayexpress

Gene expression profile of sporadic and PSEN1 early-onset Alzheimer’s Disease

Project description:Alzheimer’s disease (AD) is the most common neurodegenerative dementia. Around 10% of cases present an age of onset before 65 years-old, which in turn can be divided in monogenic or familial AD (FAD) and sporadic early-onset AD (EOAD). Mutations in PSEN1, PSEN2 and APP genes have been linked with FAD. The aim of our study was to describe the brain whole-genome RNA expression profile of the posterior cingulate area in EOAD and FAD caused by PSEN1 mutations (FAD-PSEN1). 14 patients (7 EOAD and 7 FAD-PSEN1) and 7 neurologically healthy controls were selected and samples were hybridized in a Human Gene 1.1 microarray from Affymetrix. When comparing controls with EOAD and controls with FAD-PSEN1, we found 3183 and 3351 differentially expressed genes (DEG) respectively (FDR corrected p<0.05). However, any DEG was found in the comparison of the two groups of patients. Microarrays were validated through quantitative-PCR of 17 DEG. In silico analysis of the DEG revealed an alteration in biological pathways related to calcium-signaling, axon guidance and long-term potentiation (LTP), among others, in both groups of patients. These pathways are mainly related with cell signalling cascades, synaptic plasticity and learning and memory processes. In conclusion, the altered biological final pathways in EOAD and FAD-PSEN1 are highly coincident. Also, the findings are in line with those previously reported for late-onset AD (LOAD, onset >65 years-old), which implies that the consequences of the disease at the molecular level are similar in the final stages of the disease. 21 Samples were analyzed: 7 controls, 7 Early-onset Alzheimer's disease (AD) patients and 7 early-onset AD genetically determined by a mutation in PSEN1 gene.

2015-01-20 | E-GEOD-39420 | biostudies-arrayexpress

Human iPSC-derived heart organoids modeling the etiology of pregestational diabetes induced congenital heart defects

Project description:Human iPSC-derived organoids modeling the etiology of pregestational diabetes induced congenital heart defects

2023-08-07 | GSE201343 | GEO

β2-adrenergic agonists rescue lysosome acidification and function in PSEN1 deficiency by reversing defective ER to lysosome delivery of ClC-7

Project description:Lysosomal dysfunction is considered pathogenic in Alzheimer Disease (AD). Loss of Presenilin-1(PSEN1) function causing early onset AD impedes acidification via defective vATPase V0a1 subunit delivery to lysosomes. We report that isoproterenol and related β2-adrenergic agonists re-acidify lysosomes in PSEN1 KO cells and fibroblasts from PSEN1 familial AD(FAD) patients, restores lysosomal calcium homeostasis and proteolysis, and reverses impaired autophagy flux. We identify a novel rescue mechanism involving PKA-mediated facilitated delivery of ClC-7 to lysosomes, which stimulates chloride influx and reverses markedly lowered Cl- content of PSEN1 KO lysosomes. Notably, PSEN1 loss-of-function impedes ER-to-lysosome delivery of ClC-7, thus accounting for lysosomal Cl- deficits that compound pH deficits due to deficient vATPase function. Transcriptomics of PSEN1-deficient cells reveal strongly down-regulated ER-to-lysosome transport pathways and reversibility by isoproterenol. Our findings uncover a broadened PSEN1 role in lysosomal ion homeostasis and novel pH modulation of lysosomes through β-adrenergic regulation of ClC-7, which can be therapeutically modulated.

2020-02-29 | GSE136894 | GEO

Modeling early-onset sporadic Alzheimer’s disease using iPSC-derived neurons

Project description:Non-familial Alzheimer’s disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer’s disease (EOAD) and constitutes ~5-6% of all Alzheimer’s disease (AD) cases. While EOAD exhibits the same clinicopathological changes such as amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, and cognitive decline as observed in the more prevalent late-onset AD (LOAD), EOAD patients tend to have more severe cognitive deficits, including visuospatial, language, and motor dysfunction. Patient-derived induced pluripotent stem cells (iPSCs) have been used to model and study penetrative, familial AD (FAD) mutations in APP, PSEN1, and PSEN2, but have been seldom used for sporadic forms of AD that display more heterogeneous disease manifestation. In this study, we sought to characterize iPSC-derived neurons from EOAD patients via RNA-sequencing. A modest difference in expression profiles between EOAD patients and non-demented control subjects resulted in a limited number of differentially expressed genes (DEGs). Based on this analysis, we provide evidence that iPSC-derived neuron model systems, likely due to the loss of EOAD-associated epigenetic signatures during the iPSC reprogramming, are not an ideal model system to study sporadic AD.

2023-11-21 | GSE231341 | GEO

APOE3Christchurch modulates tau phosphorylation and β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases

Project description:Alzheimer’s disease (AD) is the most common cause of dementia. A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) was found to have extreme resistance to cognitive decline and tauopathy despite having high amyloid burden. We established induced pluripotent stem cell (iPS)-derived cerebral organoids from this resistant case and a non-protected control. We used CRISPR/Cas9 gene editing to remove or add APOE3Ch from these iPS cells to assess causality. We found a pattern of tau phosphorylation consistent with protection in APOE3Ch cerebral organoids. We identified Cadherin and Wnt signaling regulation by APOE3Ch through scRNA-sequencing and elevated β-catenin protein in APOE3Ch organoids as a potential mediator of protection against tauopathy. We have identified that ApoE3Ch acts as a Wnt signaling enhancer. Our study found that APOE3Ch is necessary and sufficient to confer resistance to tauopathy, a hallmark of AD. This establishes the premise for development of novel, protected case-inspired therapeutics for AD and tauopathies.

2024-03-20 | GSE241453 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data