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GSE71194
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Muscle Expression of SOD1(G93A) Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that 50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesionedbut not normaladult white matter. We report that -catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of -catenin in the oligodendrocyte lineage in vivo and (2) findings from APCMin mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.
Publication Title
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of but not of adjacent motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.
Publication Title
Astrocyte-encoded positional cues maintain sensorimotor circuit integrity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Clinically isolated syndrome (CIS) refers to the earliest clinical manifestation of multiple sclerosis (MS). Currently there are no prognostic biological markers that accurately predict conversion of CIS to clinically definite MS (CDMS). Furthermore, the earliest molecular events in MS are still unknown. We used microarrays to study gene expression in nave CD4+ T cells from 37 CIS patients at time of diagnosis and after one year. Supervised machine-learning methods were used to build predictive models of disease conversion. We identified 975 genes whose expression segregated CIS patients into 4 distinct subgroups. A subset of 108 genes further discriminated patients from one of these (group#1) from other CIS patients. Remarkably, 92% of patients from group #1 converted to CDMS within 9 months. Consistent downregulation of TOB1, a critical regulator of cell proliferation, was characteristic of group #1 patients. Decreased TOB1 expression at the RNA and protein levels was also confirmed in experimental autoimmune encephalomyelitis (EAE). Finally, a genetic association was observed between TOB1 variation and MS progression in an independent cohort. These results indicate that CIS patients at high risk of conversion have impaired regulation of T cell quiescence resulting in earlier activation of pathogenic CD4+ cells.
Publication Title
Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Developmental regulation of gliogenesis in the mammalian CNS is incompletely understood, in part due to a limited repertoire of lineage-specific genes. We used Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes and performed gene expression profiling of these cells. We then used this dataset to identify candidate transcription factors that may serve as glial markers or regulators of glial fate. Our analysis generated a database of developmental stage-related markers of Aldh1l1+ cells between murine embryonic day 13.5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control. Thus, this dataset represents a resource for identifying novel regulators of glial development.
Publication Title
Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We characterized monosaccharide-dependent gene expression in the Drosophila fat body using fructose and glucose. Control and high-sugar diets were compared and RNA-seq was used to identify potential target genes. Overall design: Drosophila were reared on control (0.3 M fructose or glucose) or high sugar (1.7 M fructose or glucose) diets until the wandering third instar stage. Fat bodies were isolated and RNA was extracted to determine the effects of each sugar at different concentrations on gene expression using Illumina RNA-seq.
Publication Title
Similar effects of high-fructose and high-glucose feeding in a Drosophila model of obesity and diabetes.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 26 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We compared gene expression in the Drosophila fat body on control and high-sugar diets in order to gain insight into the role of this organ during caloric overload. Differential expression analysis revealed changes in gene expression suggestive of a role for CoA metabolism in the ability to tolerate high-sugar feeding. This led us to perform biochemical and mutant studies supporting a model where CoA is limiting in the face of caloric overload. Overall design: Wild-type Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Publication Title
CoA protects against the deleterious effects of caloric overload in Drosophila.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The lack of mouse models permitting the specific ablation of tissue-resident macrophages and monocyte-derived cells complicates understanding of their contribution to tissue integrity and to immune responses. Here we use a new model permitting diphtheria-toxin (DT)-mediated depletion of those cells and in which dendritic cells are spared. We showed that the myeloid cells of the mouse ear skin dermis are dominated by a population of melanin-laden macrophages, called melanophages, that has been missed in most previous studies. By using gene expression profiling, DT-mediated ablation and parabiosis, we determined their identity including their similarity to other skin macrophages, their origin and their dynamics. Limited information exist on the identity of the skin cells responsible for long-term tattoo persistence. Benefiting of our knowledge on melanophages, we showed that they are responsible for retaining tattoo pigment particles through a dynamic process which characterization has direct implications for improving strategies aiming at removing tattoos.
Publication Title
Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene transcripts and proteins expressed during disease pathogenesis identify targets for therapy. We performed microarray analysis of histologically characterized multiple sclerosis (MS) brain lesions in comparison with control brain samples to identify differentially expressed molecules. We identified CD47 as a target of interest and studied its biology in MS and EAE.
Publication Title
Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine Cytomegalovirus (MCMV) infection leads to early activation of various immune cells, including B and T lymphocytes, before the actual initiation of antigen-specific adaptive immunity. This activation is partly driven by innate cytokines, including type I interferon (IFN), which are induced early after infection. The objective of this study was to address the role of type I IFN in shaping early/innate B and T cell responses to a primary acute viral infection.
Publication Title
Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation.
Sample Metadata Fields
Specimen part
View Samples