Project description:Fmr1 mutation results in autistic behaviors and the FMR1 KO mice model is one of the popular methods to study autism spectrum disorders. In this dataset, we include the expression data obtained from astrocytes isolated from cortex of control and FMR1-KO mice.
Project description:Fragile X syndrome and tuberous sclerosis are genetic syndromes that both have a high rate of co-morbidity with autism spectrum disorders. Several lines of evidences suggest that these two monogenic disorders may converge at a molecular level through the dysfunction of activity-dependent synaptic plasticity. We utilized mouse models of these monogenic disorders to identify genome-wide transcriptional changes in cerebellum and blood and characterize the (dis-)similarity of their molecular signatures. Differentially expressed genes and enriched pathways were distinct for the two mouse models examined, with the exception of immune system related pathways. In the cerebellum of the Fmr1 knockout (Fmr1-KO) model, the neuroactive ligand receptor interaction pathway and gene sets associated with synaptic plasticity such as long term potentiation, gap junction, and axon guidance were the most significantly perturbed pathways. The phosphatidylinositol signaling pathway was significantly dysregulated in both blood and brain of Fmr1-KO mice. In both the blood and brain of the Tsc2 heterozygous mouse model, immune system related pathways, genes encoding ribosomal proteins, and glycolipid metabolism pathways were significantly perturbed. Our data suggest that distinct molecular pathways may be involved in autism spectrum disorders with known but different genetic causes, and that blood gene expression profiles of Fmr1-knockout and Tsc2+/- mice mirror some, but not all, of the perturbed molecular pathways in the brain. For the Fmr1-KO model, 10 mice, consisting of 5 KO and 5 WT mice, were profiled. Thus, 10 pairs of blood and cerebella samples were profiled. Likewise, for the Tsc+/- model, 3 transgenic and 3 WT mice were sacrificed and paired blood and cerebella samples were prepared for gene expression profiling. All samples were profiled using the Affymetrix Mouse Gene ST 1.0 ST arrays. Three factors—tissue (i.e. blood vs. cerebellum), treatment (i.e. knockout vs. wildtype), and genetic background (Fmr1-KO vs. Tsc2+/-)—were analyzed with analysis of variance (ANOVA). Subsequently, we compared blood and brain gene expression changes in Fmr1 and Tsc2 knockout mice models using WT littermates as controls using t-tests with unequal variances. The false discovery rate (FDR) was calculated using Storey and Tibshirani’s method.
Project description:Transcriptional profiling of FACS-sorted and splenic control mouse cells, comparing splenic cells from FVBneuN vs Neu+ expressing FVBneuN mice with Gr1+ CD11b+ sorted tumor-infiltrating mononuclear or splenic myeloid-derived suppressor cells
Project description:TRAP (translating ribosome affinity purification) from CA1 pyramidal neurons and cerebellar granule cells in wildtype and Fmr1 KO littermate pairs. These data show a global downregulation of FMRP targets in Fmr1 KO mice in these cell types.
Project description:Dysfunction of astrocytic support for prolonged time can be harmful for nervous system. Inflammation and glia activation are among hallmarks of most neurodegenerative diseases. Therefore, astrocytes are considered as druggable targets for disease modifying strategies. Partial lesion of dopaminergic neurons is compensated functionally, but which mechanisms within each type of cells are responsible is unknown. The aim was to check how neuron vs astrocyte degeneration affected remaining astrocytes proteome and which mechanisms were regulated. In a rat model of 7-day infusion by osmotic minipumps of fluorocitrate (FC) into the substantia nigra (SN) (doi: 10.1007/s12035-017-0529-z; doi: 10.1111/jnc.14605; doi: 10.1016/j.mito.2018.12.002) astrocytes become dysfunctional and die inducing activation of remaining astrocytes and microglia. 6-OHDA injected into medial forebrain bundle caused selective degeneration of dopaminergic neurons in the SN. Controls were sham operated. Astrocytes were sorted out from dissociated SN tissue using FACS, and processed for mass spectrometry proteome analysis. Understanding the role of individual cell type in the diseased tissue cellular context is essential to understand disease pathomechanisms and identify better pharmacological targets.
Project description:Nervous system inflammation and microglia activation are among hallmarks of Parkinson’s disease. Partial nigrostriatal neurodegeneration can be compensated. Interaction between neurons, microglia and astrocytes could be essential for this functional adaptation and neuronal survival in long-term, but which mechanisms are responsible is unknown. The aim was to check how astrocyte vs neuron degeneration affected differentially microglia activation proteome and which mechanisms were regulated. In a rat model of 7-day infusion by osmotic minipumps of fluorocitrate (FC) into the substantia nigra (SN) (doi: 10.1007/s12035-017-0529-z; doi: 10.1111/jnc.14605; doi: 10.1016/j.mito.2018.12.002) astrocytes become dysfunctional and die, strongly activating microglia in the process. 6-OHDA injected into medial forebrain bundle caused selective degeneration of dopaminergic neurons in the SN and only slightly activated microglia, probably via different mechanism. Controls were sham operated. Microglia cells were sorted out from dissociated SN tissue using FACS, and processed for mass spectrometry proteome analysis. Microglial response to dying astrocytes vs dying neurons was different. Understanding the role of individual cell type in the diseased tissue cellular context is essential to understand disease pathomechanisms and identify better pharmacological targets.
Project description:To investigate TFEB-dependent mRNA expression in murine B cells, FACS-sorted germinal center and non-germinal center B lymphocytes of B-cell-specific conditional TFEB KO mice and control littermates were subjected to RNA sequencing analysis
Project description:The experiment was performed to identify autophagy targets in wildtype and autophagy-deficient forebrain inhibitory neurons. Therefore, neurons were isolated from the cortex, hippocampus and striatum of 2-3 weeks old Atg5flox/flox:Slc32a1-Cretg/wt:tdTomato+ (KO) and Atg5wt/wt:Slc332a1-Cretg/wt:tdTomato+ (WT) mice. Neurons in suspension were FACS sorted and inhibitory forebrain neurons expressing tdTomato were forwarded to global proteome analysis assessed by LC-MS/MS.
Project description:The experiment was performed to identify autophagy targets in wildtype and autophagy-deficient forebrain excitatory neurons. Therefore, neurons were isolated from the cortex, hippocampus and striatum of 2-3 weeks old Atg5flox/flox:CamKIIα-Cretg/wt:tdTomato+ (KO) and Atg5wt/wt:CamKIIα-Cretg/wt:tdTomato+ (WT) mice. Neurons in suspension were FACS sorted and excitatory forebrain neurons expressing tdTomato were forwarded to global proteome analysis assessed by LC-MS/MS.