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Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [scRNA-seq]

ABSTRACT: Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [scRNA-seq]

PROVIDER: PRJNA1077347 | ENA |

REPOSITORIES: ENA

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Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [BiSulfite-seq]

Project description:Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) resets the aging clock and is thought to erase other epigenomic marks. Here we show that iPSCs from late-onset sporadic Alzheimer’s disease (AD) cases retain epigenomic anomalies that supersede developmental defects, genomic instability, and neurodegeneration. When compared to iPSCs from elderly controls, AD iPSCs display reduced BMI1 and KDM5A expression, a more relax heterochromatin, and an altered DNA methylome. AD neuroepithelial cells show lesser efficient neural induction and forebrain specification, together with perturbed WNT signaling. They also present a unique genomic instability phenotype characterized by replication stress and DNA damage at the nuclear envelope-associated heterochromatin. BMI1 knockdown in control neuroepithelial cells phenocopied the AD-related pathologies. Long-term AD neuronal cultures show a dedifferentiation and loss-of-cell identity phenotype resembling epigenome erosion. BMI1 overexpression in AD neurons mitigates amyloid accumulation, tau pathology, heterochromatin fragmentation and G4 DNA induction. These findings implicate persistent epigenomic anomalies or uncharacterized genetic alterations working in trans on the epigenome in AD iPSCs, which could have broader implications in our understanding of the disease origin and pathophysiological mechanisms.

2024-07-30 | GSE255983 | GEO

Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [RNA-seq]

2024-07-30 | GSE255982 | GEO

Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [scRNA-seq]

2024-07-30 | GSE255981 | GEO

Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases

Project description:Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases

| PRJNA1077342 | ENA

Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [RNA-seq]

Project description:Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [RNA-seq]

| PRJNA1077346 | ENA

Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [BiSulfite-seq]

Project description:Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases [BiSulfite-seq]

| PRJNA1077353 | ENA

Persistent epigenome anomalies in induced pluripotent stem cells from late-onset sporadic Alzheimer’s disease cases

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-07-30 | GSE255985 | 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

Exome sequencing of chordoma families and sporadic cases

Project description:Exome sequencing of chordoma families and sporadic cases

| PRJNA369586 | ENA

Mitochondrial anomalies in induced pluripotent stem cells from Alzheimer’s disease cases with Presenilin 1 mutation

Project description:Mitochondrial anomalies in induced pluripotent stem cells from Alzheimer’s disease cases with Presenilin 1 mutation

| PRJNA1065335 | ENA