Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1253117 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenetic-mediated gene regulation orchestrates brain cell-type gene expression programmes, and epigenetic dysregulation is a major driver of aging and disease-associated changes. Proteins that mediate gene regulation are mostly localised to the nucleus, however, nuclear-localised proteins are often under-represented in gene expression studies and have been understudied in the context of the brain. To address this challenge, we have optimised an approach for nuclei isolation that is compatible with proteomic analysis. This was coupled to a mass spectrometry protocol for detecting proteins in low-concentration samples. We have generated nuclear proteomes for neurons, microglia, and oligodendrocytes from the mouse brain cortex and identified cell-type nuclear proteins associated with chromatin structure and organisation, chromatin modifiers such as transcription factors, and RNA-binding proteins, among others. Our nuclear proteomics platform paves the way for assessing brain cell type changes in the nuclear proteome across health and disease, such as neurodevelopmental, aging, neurodegenerative, and neuroinflammatory conditions.
2024-08-09 | PXD053515 | Pride
Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
2024-02-23 | GSE241559 | GEO
Project description:Here, we have developed a novel methodology called IRIS (Imaging Reconstruction using Indexed Sequencing) that enables cost-effective spatial transcriptomics profiling without relying on optical imaging. Through neighborhood interaction-based reconstruction, IRIS allows extensive analysis of large tissue sections and many replicates with adjustable mapping resolution at only a fraction of the cost of other commercial platforms. With the IRIS platform, we reconstructed a large area spatial area with two whole mouse brain coronal sections. Moreover, we also created a spatially resolved transcriptome atlas of the mouse brain and identified aging-associated changes in gene expression and spatial organization across various brain cell types. Further analysis of cell-cell interaction changes identified aging-associated foci in white matter regions enriched with inflammatory subtypes of microglia and oligodendrocytes. Overall, the IRIS methodology cost-effective and ease-of-use approach makes it broadly applicable to the studies of spatial gene expression changes in various systems.
2024-09-12 | GSE270383 | GEO
Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
2024-02-23 | GSE241560 | GEO
Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
2024-02-23 | GSE243678 | GEO
Project description:A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. Here, we found age-related alterations of oligodendrocytes with a reduction of total oligodendrocyte density in the aging murine white matter. Using single-cell RNA sequencing, we identify interferon-responsive oligodendrocytes, which localize in proximity of CD8+ T cells in the aging white matter. Absence of functional lymphocytes decreased oligodendrocyte reactivity and rescued oligodendrocyte loss, while T-cell checkpoint inhibition worsened the aging effect. In addition, we identified a subpopulation of immune cell dependent interferon-responsive microglia in the aging white matter, and co-culture experiments revealed that interferon- activated microglia triggered oligodendrocytes cell death. In summary, we provide evidence that T cells induced interferon-responsive oligodendrocytes and microglia are important modifiers of white matter aging.
2022-09-13 | GSE202579 | GEO
Project description:LysoIP experiment using different Cre-lines to characterize the lysosomal content of the brain. Using Syn1-Cre (Neurons), Gfap-Cre (Astrocytes), Olig2-Cre (Oligodendrocytes) and Cx3cr1-Cre (Microglia) mouse lines, to understand by MS the different composition.
2024-10-03 | MSV000096018 | MassIVE
Project description:Analysis of proteome changes during mouse brain aging
| MSV000082968 | MassIVE
Project description:Characterization of phosphorylated peptides during Mouse brain aging.
2023-12-19 | MSV000093687 | MassIVE