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Characterization of cuprizone mouse model at single-cell and spatial transcriptomics level[Spatial Transcriptomics]

ABSTRACT: We generated a comprehensive dataset utilizing the cuprizone model. This dataset encompasses bulk RNA-seq, single-nucleus RNA-seq (snRNA-seq), and spatial transcriptomics, with the aim of investigating the molecular changes linked to the cuprizone-induced demyelination phenotype. Integration of these omics dataset allowed us to investigate the changes occurring at both the single-cell and spatial levels, thereby enabling a deeper understanding of the cellular dynamics and molecular interactions associated with the cuprizone-induced demyelination phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE255370 | GEO | 2024/11/06

REPOSITORIES: GEO

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Characterization of cuprizone mouse model at single-cell and spatial transcriptomics level[snRNA-seq]

Project description:We generated a comprehensive dataset utilizing the cuprizone model. This dataset encompasses bulk RNA-seq, single-nucleus RNA-seq (snRNA-seq), and spatial transcriptomics, with the aim of investigating the molecular changes linked to the cuprizone-induced demyelination phenotype. Integration of these omics dataset allowed us to investigate the changes occurring at both the single-cell and spatial levels, thereby enabling a deeper understanding of the cellular dynamics and molecular interactions associated with the cuprizone-induced demyelination phenotype.

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Characterization of cuprizone mouse model at single-cell and spatial transcriptomics level[Spatial Transcriptomics]

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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 miRNA expression in CPZ-induced demyelination compared with control, we performed the Affymetrix GeneChip® miRNA 4.0 Array. We identified 1348 and 1253 differentially expressed miRNAs for control and CPZ-treated mice, respectively. Furthermore, the expression of 240 miRNAs was significantly changed in CPZ-induced mice comparing with control mice. These results suggest that the changes of miRNA expression in vivo may provide a new potential remyelination therapeutic target.

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Project description:Spatial organization of different cell types within prenatal skin across various anatomical sites is not well understood. To address this, here we have generated spatial transcriptomics data from prenatal facial and abdominal skin obtained from a donor at 10 post conception weeks. This in combination with our prenatal skin scRNA-seq dataset has helped us map the location of various identified cell types.

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Dynamics of reactive astrocytes fosters tissue regeneration after cuprizone-induced demyelination [RNA-seq II]

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.

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