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Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [Hi-C]

ABSTRACT: Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [Hi-C]

PROVIDER: PRJNA945057 | ENA |

REPOSITORIES: ENA

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Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration

Project description:Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration

| PRJNA945060 | ENA

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [BLISS]

Project description:Persistent DNA double-strand breaks (DSBs) in neurons are an early pathological hallmark of neurodegenerative diseases including Alzheimer’s Disease (AD), with the potential to disrupt genome integrity. We used single-nucleus RNA-seq in human post-mortem prefrontal cortex samples and found that excitatory neurons in AD were enriched for somatic mosaic gene fusions. Gene fusions were particularly enriched in excitatory neurons with DNA damage repair and senescence gene signatures. In addition, somatic genome structural variations and gene fusions were enriched in neurons burdened with DSBs in the CK-p25 mouse model of neurodegeneration. Neurons enriched for DSBs also had elevated levels of cohesin along with progressive multiscale disruption of the 3D genome organization aligned with transcriptional changes in synaptic, neuronal development, and histone genes. Overall, this study demonstrates the disruption of genome stability and the 3D genome organization by DSBs in neurons as pathological steps in the progression of neurodegenerative diseases.

2023-09-27 | GSE227438 | GEO

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [BLISS]

Project description:Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [BLISS]

| PRJNA945055 | ENA

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [Mate-Pair]

Project description:Persistent DNA double-strand breaks (DSBs) in neurons are an early pathological hallmark of neurodegenerative diseases including Alzheimer’s Disease (AD) with the potential to disrupt genome integrity. We show increased mosaic structural variations and gene fusions in neurons burdened with DSBs in the CK-p25 inducible mouse model of neurodegeneration. Next, we used full-transcript single-nucleus RNA-seq across 47 human post-mortem prefrontal cortex and find that excitatory neurons in AD are enriched for mosaic gene fusions. In addition, gene fusions are particularly enriched in excitatory neurons with senescence and DNA repair gene signatures. Neurons enriched for DSBs also have elevated levels of cohesin along with progressive multiscale disruption of the 3D genome organization aligned with transcriptional changes in synaptic and neuronal development genes. Overall, this study demonstrates the disruption of genome stability and the 3D genome organization by DSBs in neurons as pathological steps in the progression of neurodegenerative diseases.

2023-09-27 | GSE227444 | GEO

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [Hi-C]

2023-09-27 | GSE227443 | GEO

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [Mate-Pair]

Project description:Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [Mate-Pair]

| PRJNA945061 | ENA

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration.

Project description:Persistent DNA double-strand breaks (DSBs) in neurons are an early pathological hallmark of neurodegenerative diseases including Alzheimer's disease (AD), with the potential to disrupt genome integrity. We used single-nucleus RNA-seq in human postmortem prefrontal cortex samples and found that excitatory neurons in AD were enriched for somatic mosaic gene fusions. Gene fusions were particularly enriched in excitatory neurons with DNA damage repair and senescence gene signatures. In addition, somatic genome structural variations and gene fusions were enriched in neurons burdened with DSBs in the CK-p25 mouse model of neurodegeneration. Neurons enriched for DSBs also had elevated levels of cohesin along with progressive multiscale disruption of the 3D genome organization aligned with transcriptional changes in synaptic, neuronal development, and histone genes. Overall, this study demonstrates the disruption of genome stability and the 3D genome organization by DSBs in neurons as pathological steps in the progression of neurodegenerative diseases.

| S-EPMC10697236 | biostudies-literature

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration

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

2023-09-27 | GSE227445 | GEO

Neurons burdened by DNA double strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration.

Project description:DNA double strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. Here, we characterize DSB-bearing neurons from the CK-p25 mouse model of neurodegeneration using single-nucleus, bulk, and spatial transcriptomic techniques. DSB-bearing neurons enter a late-stage DNA damage response marked by NFκB-activated senescent and antiviral immune pathways. In humans, Alzheimer’s disease pathology is significantly associated with immune activation in excitatory neurons. Spatial transcriptomics reveal that regions of CK-p25 brain tissue dense with DSB-bearing neurons harbor signatures of inflammatory microglia, which is ameliorated by NFκB knock-down in neurons. Inhibition of NFκB in DSB-bearing neurons also reduces microglia activation in organotypic mouse brain slice culture. In conclusion, DSBs activate immune pathways in neurons, which in turn adopt a senescence-associated secretory phenotype to elicit microglia activation. These findings highlight a novel role for neurons in the mechanism of disease-associated neuroinflammation.

2022-05-10 | GSE174265 | GEO

DNA double-strand breaks and 3D chromatin conformation (ChIP-chip)

Project description:DNA Double-Strand Breaks (DSBs) are highly detrimental since they can lead to mutations and chromosomes rearrangements (amplification, deletion, translocation and chromosome loss). ChIP-chip of P-SMC3 (S1083) and P-SMC1 (S966) were used to show the recruitment of these marks on DNA repair foci. ChIP-chip of gammaH2AX upon CRISPR induction at different positions within a single TAD was also performed.

2021-01-29 | E-MTAB-8793 | biostudies-arrayexpress

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