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Cellular rejuvenation protects neurons from inflammation mediated cell death (ATAC-seq).

ABSTRACT: Cellular rejuvenation protects neurons from inflammation mediated cell death (ATAC-seq).

PROVIDER: PRJNA1034145 | ENA |

REPOSITORIES: ENA

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Cellular rejuvenation protects neurons from inflammation mediated cell death (RNA-seq).

Project description:Cellular rejuvenation protects neurons from inflammation mediated cell death (RNA-seq).

| PRJNA1036568 | ENA

Cellular rejuvenation protects neurons from inflammation mediated cell death (RNA-seq).

Project description:In multiple sclerosis (MS), invasion of the central nervous system by peripheral immune cells, activation of resident microglia and astrocytes, and demyelination occur as a cascade of events that trigger neuronal damage and death. The molecular signals in neurons that activate damage in response to the complex immune environment have not been fully characterized. Retinal ganglion cell neurons (RGCs) of the central nervous system (CNS) undergo axonal injury and cell death in MS and this is recapitulated in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. To profile the molecular landscape of pathologically inflamed neurons, we isolated RGCs from mice that were subjected to the EAE protocol and performed RNA-sequencing and ATAC-sequencing analysis. Pathway analysis of the RNA-sequencing data revealed that RGCs exhibited a molecular signature reminiscent of aged neurons with features of senescence. Pathway level analysis of single-nucleus RNA-sequencing analysis of human MS neurons also demonstrated a similar senescence-like phenotype. Immunofluorescence analyses confirmed alterations to various markers of senescence in RGCs in EAE mice, including alterations to the nuclear envelope, changes to chromatin marks, and accumulation of DNA damage. Transduction of RGCs with an Oct4-Sox2-Klf4 transgene to rejuvenate neurons to a younger epigenetic and transcriptomic state in the EAE model was sufficient to increase survival of RGCs. Together, this work reveals a novel senescent like phenotype in neurons in a model of pathological inflammation and in neurons from MS patients. Rejuvenation of the aged transcriptome improves visual acuity and neuronal survival in the EAE model supporting the notion that anti-aging therapies and/or senotherapeutic agents may directly target neurons for neuroprotection in autoimmune disorders.

2025-01-01 | GSE247173 | GEO

Cellular rejuvenation protects neurons from inflammation mediated cell death (ATAC-seq).

2025-01-01 | GSE246702 | GEO

Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation

Project description:Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation

| PRJNA994501 | ENA

Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (RNA-Seq)

2024-03-20 | GSE237269 | GEO

Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (Hi-C)

Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional and genome-wide chromatin organization changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state, showed a reorganization of the inter-chromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased contractility and reduced chromosome copy number variations, similar to younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.

2024-03-20 | GSE237268 | GEO

Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (RNA-Seq)

Project description:Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (RNA-Seq)

| PRJNA994507 | ENA

Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (Hi-C)

Project description:Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (Hi-C)

| PRJNA994504 | ENA

Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation

Project description:Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation

| PRJNA318003 | ENA

PD-1 Protects Bystander-Activated T Cells from Activation-Induced Cell Death

Project description:PD-1 is a critical T-cell checkpoint that suppresses nonantigen-specific bystander memory T-cell activation and proliferation but also protects them from apoptotic activation-induced cell death.

2023-10-25 | GSE199615 | GEO

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