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Age-Related Injury Responses of Human Oligodendrocytes to Metabolic Insults: Link to BCL-2 and Autophagy Pathways

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160813 | GEO | 2020/12/31

REPOSITORIES: GEO

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Project description: Not available

| S-EPMC7782481 | biostudies-literature

Project description:Myelin destruction and oligodendrocyte (OL) death consequent to metabolic stress is a feature of CNS disorders across the age spectrum. Using cells derived from surgically resected tissue, we demonstrate that young (<age 5) pediatric-aged sample OLs are more resistant to in-vitro metabolic injury than fetal O4+ progenitor cells, but more susceptible to cell death and apoptosis than adult-derived OLs. Pediatric but not adult OLs show measurable levels of TUNEL+ cells, a feature of the fetal cell response. The ratio of anti- versus pro-apoptotic BCL-2 family genes are increased in adult versus pediatric (<age 5) mature OLs and in more mature OL lineage cells. Lysosomal gene expression was increased in adult and pediatric compared to fetal OL lineage cells. Cell death of OLs was increased by inhibiting pro-apoptotic BCL-2 gene and autophagy activity. These distinct age-related injury responses should be considered in designing therapies aimed at reducing myelin injury.

2020-12-31 | GSE160811 | GEO

2020-12-31 | GSE160810 | GEO

Project description:Age-Related Injury Responses of Human Oligodendrocytes to Metabolic Insults: Link to BCL-2 and Autophagy Pathways

| PRJNA674571 | ENA

Project description:Age-Related Injury Responses of Human Oligodendrocytes to Metabolic Insults: Link to BCL-2 and Autophagy Pathways [Microarray]

| PRJNA674579 | ENA

Project description:Age-Related Injury Responses of Human Oligodendrocytes to Metabolic Insults: Link to BCL-2 and Autophagy Pathways [RNA-seq]

| PRJNA674580 | ENA

Dor regulates alpha-KG metabolic pathways in mature oligodendrocytes to enhance myelination and reverse age-related remyelination decline

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

2024-07-04 | GSE233593 | GEO

Dor regulates alpha-KG metabolic pathways in mature oligodendrocytes to enhance myelination and reverse age-related remyelination decline [RNA-seq]

Project description:Impairment of oligodendrocyte (OL) myelinogenic potential, rather than inability of oligodendrocyte precursors to differentiate, is implicated in remyelination failure in demyelinating diseases such as multiple sclerosis. However, the mechanisms underlying myelinogenesis and age-related decline in remyelination remain elusive. Here, we identify a mature-OL-active transcriptional regulator Dor as a critical mediator of CNS myelination and remyelination. Genomic occupancy and transcriptomic analyses revealed that Dor interacts with Sox10 and targets the enhancers of myelinogenesis-regulatory genes including a newly identified OL-enriched nuclear factor Prr18 required for OL maturation. Metabolomic profiling showed that Dor is critical for alpha-ketoglutarate (alpha-KG) production and lipid biosynthesis. Supplementation with alpha-KG enhanced lipid biosynthesis and restored OL maturation defects in Dor-mutant mice while reversing the age-associated decline in remyelination efficiency and memory deficits in aging mice. Thus, our findings connect the OL-active Dor regulatory activity to alpha-KG-mediated lipid metabolism in mature OLs to thereby facilitate myelin production and remyelination.

2024-07-05 | GSE233592 | GEO

Dor regulates alpha-KG metabolic pathways in mature oligodendrocytes to enhance myelination and reverse age-related remyelination decline [CUT&Tag]

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Dor regulates alpha-KG metabolic pathways in mature oligodendrocytes to enhance myelination and reverse age-related remyelination decline [RNA-seq II]

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