Transcriptomic profiling of oligodendrocytes, astrocytes, and microglia in a cuprizone-induced demyelination model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1212138 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Demyelination is a central pathological feature of multiple sclerosis and many other neurodegenerative diseases, and the cuprizone diet is a widely used model for studying this process. This study examines the transcriptional changes in key glial cell types—oligodendrocyte and astrocytes—during demyelination induced by a 4-week cuprizone diet. Bulk RNA sequencing was performed on these cells isolated using magnetic-activated cell sorting (MACS) from mice on either a normal diet or a 0.3% cuprizone diet. The experimental groups included: (1) oligodendrocytes and astrocytes from mice on a normal diet, and (2) oligodendrocytes and astrocytes from mice on a cuprizone diet. This study provides a comprehensive transcriptomic view of how these glial cell types respond to demyelination and will enhance our understanding of their individual and collective roles in this pathological process.
2025-08-17 | GSE287320 | GEO
Project description:We examined the role of TREM2 on microglia responses to demyelination Microglia were FACS-purified from WT or Trem2-/- mice fed with 0.2% cuprizone diet.
2015-04-22 | E-GEOD-66926 | biostudies-arrayexpress
Project description:Demyelination and dysregulated myelination in the CNS are hallmarks of many neurodegenerative diseases such as multiple sclerosis (MS) and leukodystrophies. Here, we studied GFAP+ astrocytes during de- and remyelination in the cuprizone mouse by exploiting the ribosomal tagging (RiboTag) technology. Analyses were performed 5 weeks after cuprizone feeding, at the peak of demyelination in the corpus callosum, and 0.5 and 2 weeks after cuprizone withdrawal, when remyelination and tissue repair is initiated. After 5 weeks of cuprizone feeding, reactive astrocytes showed inflammatory signatures with enhanced expression of genes that modulate leukocyte migration (Tlr2, Cd86, Parp14,Cxcl10). Furthermore, demyelination-induced reactive astrocytes expressed numerous ligands including Cx3cl1, Csf1, Il34, and Gas6 that act on homeostatic as well as activated microglia and thus potentially mediate activation and recruitment of microglia as well as enhancement of their phagocytosis. During early remyelination, region-specific astrocytes displayed reduced inflammatory response signatures as indicated by shut down of CXCL10 production. During late remyelination, the signatures of GFAP+ astrocytes shifted towards resolving inflammation by active suppression of lymphocyte activation and differentiation and support of glia cell differentiation. Astrocytes showed enhanced expression of osteopontin (SPP1) as well as of factors that are relevant for tissue remodelling (Timp1), regeneration and axonal repair. In conclusion, we detected highly dynamic astroglial transcriptomic signatures in the cuprizone model, which reflects excessive communication amongst glia cells and highlights different astrocyte functions during neurodegeneration and regeneration.
2023-07-11 | GSE236805 | GEO
Project description:Demyelination and dysregulated myelination in the CNS are hallmarks of many neurodegenerative diseases such as multiple sclerosis (MS) and leukodystrophies. Here, we studied GFAP+ astrocytes during de- and remyelination in the cuprizone mouse by exploiting the ribosomal tagging (RiboTag) technology. Analyses were performed 5 weeks after cuprizone feeding, at the peak of demyelination in the corpus callosum, and 0.5 and 2 weeks after cuprizone withdrawal, when remyelination and tissue repair is initiated. After 5 weeks of cuprizone feeding, reactive astrocytes showed inflammatory signatures with enhanced expression of genes that modulate leukocyte migration (Tlr2, Cd86, Parp14,Cxcl10). Furthermore, demyelination-induced reactive astrocytes expressed numerous ligands including Cx3cl1, Csf1, Il34, and Gas6 that act on homeostatic as well as activated microglia and thus potentially mediate activation and recruitment of microglia as well as enhancement of their phagocytosis. During early remyelination, region-specific astrocytes displayed reduced inflammatory response signatures as indicated by shut down of CXCL10 production. During late remyelination, the signatures of GFAP+ astrocytes shifted towards resolving inflammation by active suppression of lymphocyte activation and differentiation and support of glia cell differentiation. Astrocytes showed enhanced expression of osteopontin (SPP1) as well as of factors that are relevant for tissue remodelling (Timp1), regeneration and axonal repair. In conclusion, we detected highly dynamic astroglial transcriptomic signatures in the cuprizone model, which reflects excessive communication amongst glia cells and highlights different astrocyte functions during neurodegeneration and regeneration.
2023-07-11 | GSE233951 | GEO
Project description:The experimental autoimmune encephalomyelitis (EAE) mouse model is widely used to study the pathophysiology of multiple sclerosis (MS), including brain inflammation and demyelination. This study investigates cell-type-specific transcriptional changes in oligodendrocytes, astrocytes, and microglia at day 30 post-induction of EAE using MOG peptide (amino acids 35–55) emulsified in complete Freund’s adjuvant (CFA) containing Mycobacterium tuberculosis, followed by pertussis toxin injections. CFA control mice received only CFA and pertussis toxin, without MOG peptide. Oligodendrocytes, astrocytes, and microglia were isolated using magnetic-activated cell sorting (MACS) from brain and spinal cord of CFA-treated and EAE-induced mice. Bulk RNA sequencing was conducted to uncover transcriptional changes associated with EAE-induced demyelination. These findings will enhance our understanding of glial cell contributions to MS pathogenesis and help identify potential therapeutic targets.
2025-08-17 | GSE287323 | GEO
Project description:How microglia respond and regulate demyelination is not fully understood. To understand how microglia respond during demyelination, we fed mice cuprizone and assessed the response of genetically fate-mapped microglia. Cuprizone-induced demyelination generated a robust microglial response. We conducted single-cell RNA sequencing and identified several cuprizone-associated microglia (CAM) clusters during demyelination. These clusters expressed a transcriptomic signature indicative of cytokine regulation and reactive oxygen species production with altered lysosomal and metabolic changes consistent with ongoing phagocytosis. To understand how microglia contribute to the clearance of dead oligodendrocytes, we ablated microglia starting at the peak of cell death. We used the viability dye acridine orange and monitored apoptotic and lytic cell morphologies after microglial ablation and found that microglia preferentially phagocytose lytic carcasses. In culture, microglia exposed to lytic carcasses partially recapitulated the CAM state, suggesting that phagocytosis contributes to this distinct microglial state during cuprizone demyelination.
2022-08-08 | GSE207570 | GEO
Project description:Dynamics of reactive astrocytes fosters tissue regeneration after cuprizone-induced demyelination
| PRJNA993135 | ENA
Project description:Microglia, the primary immune cells of the central nervous system, play critical roles in demyelination process. This study investigates the transcriptional changes in microglia associated with demyelination and examines the role of oligodendrocyte-secreted Serpina3n in modulating microglial responses during this pathological process. Bulk RNA sequencing was conducted on microglia isolated from mice subjected to a 4-week cuprizone diet, a model of demyelination. The experimental groups included: (1) normal control mice (Norm_Ctrl), (2) cuprizone-treated wild-type mice (CPZ_Ctrl), and (3) cuprizone-treated Olig2-Cre Serpina3n flox/flox mice (CPZ_cKO). Microglia were purified from mouse brains using magnetic-activated cell sorting (MACS). The results of this study aim to deepen our understanding of olidodendroglial Serpina3n’s role in shaping microglial behavior during demyelination and could inform potential therapeutic strategies for demyelinating diseases.
2025-08-17 | GSE287313 | GEO
Project description:Transcriptomic profiling of oligodendrocytes, astrocytes, and microglia in an experimental autoimmune encephalomyelitis (EAE) model of demyelination
| PRJNA1212135 | ENA
Project description:Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). The neurotoxicant cuprizone (CPZ) has been extensively used to create a mouse model of demyelination. However, the changes of miRNA expression and effects on behavior of cuprizone treatment have not been clearly reported. We have analyzed the behavioral changes of mice given a diet containing 0.2% cuprizone for 6 weeks. To evaluate the changes of gene expression in CPZ-induced demyelination compared with control, we performed the GeneChip® mouse Gene 2.0 ST Array.
2019-03-30 | GSE129049 | GEO