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GSE11358
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcriptional dysregulation plays a major role in the pathology of Huntington's disease (HD). However, the mechanisms causing selective downregulation of genes remain unknown. Histones regulate chromatin structure and thereby control gene expression; recent studies have demonstrated a therapeutic role for histone deacetylase (HDAC) inhibitors in polyglutamine diseases. This study demonstrates that despite no change in overall acetylated histone levels, histone H3 is hypo-acetylated at promoters of downregulated genes in R6/2 mice, ST14a and STHdh cells, as demonstrated by in vivo chromatin immunoprecipitation. In addition, HDAC inhibitor treatment increases association of acetylated histones with downregulated genes and corrects mRNA abnormalities. In contrast, there is a decrease in mRNA levels in wild-type cells following treatment with a histone acetyltransferase inhibitor. Although changes in histone acetylation correlate with decreased gene expression, histone hypo-acetylation may be a late event, as no hypo-acetylation is observed in 4-week-old R6/2 mice. Nevertheless, treatment with HDAC inhibitors corrects mRNA abnormalities through modification of histone proteins and may prove to be of therapeutic value in HD.
Publication Title
Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 53 Downloadable Samples
Illumina HiSeq 2500
Description
The meningeal space is occupied by a diverse repertoire of innate and adaptive immune cells. CNS injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation in CNS injury remains poorly understood. Here we describe group 2 innate lymphoid cells (ILC2s) as a novel cell type resident in the healthy meninges that is activated following CNS injury. ILC2s are present throughout the naïve mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile relative to lung ILC2s. After spinal cord injury, meningeal ILC2s are activated in an IL-33 dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild type lung-derived ILC2s into the meningeal space of IL-33R-/- animals improves recovery following spinal cord injury. These data characterize ILC2s as a novel meningeal cell type that responds to and functionally affects outcome after spinal cord injury, and could lead to new therapeutic insights for CNS injury or other neuroinflammatory conditions. Overall design: ILC2s were isolated from 10 week C57/Bl6 mice with and without spinal cord injury (1 day post injury). 5 mice were pooled per group, with meninges dissected, digested, and FACs sorted (CD45+/DAPI-/Lin–/St2+/Thy1+) directly into RNA lysis buffer.
Publication Title
Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
- IlluminaHiSeq2500
Description
The goal of this study is to analyzed transcriptome changes caused by POLA1 deficiency. Our data represents the first detailed analysis of molecular basis of XLPDR syndrome. We report than POLA1 deficiency leads to over-activation of IRF and NF-kB pathways with overexpression of typical markers of autoimmune syndromes. Overall design: Wild type and XLPDR-derived dermal fibroblasts are analyzed under non-stimulated (basal) conditions, after TNF treatment (2 and 12 h, 1000 U/mL), and poly(dA:dT) stimulation (16h, 1 mkg/mL). Obtained data were confirmed using the cellular model of XLPDR - normal dermal fibroblasts pretreated with control or anti-POLA1 siRNA and stimulated in analogous way.
Publication Title
NK cell defects in X-linked pigmentary reticulate disorder.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina HiSeq 2500
Description
Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Microglia were isolated from the brains of adult male c57BL/6 mice given bone marrow tranplants (BMT) with or without head shield. All mice received PLX5622 for 2 weeks, then placed and normal chow to recoever. Some mice were then challenged with LPS. Cells were isolated by MACS using CD11b magnetic beads.
Publication Title
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Mice were given 1000rad whole body irradiation, followed by bone marrow transplant with UBC-GFP bone marrow at 8 weeks of age. Engraftment was allowed to occur for 8 months, then engrafting macrophages and microglia were isolated from whole brains for RNA-Seq.
Publication Title
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Epithelial-mesenchymal transition (EMT) has been linked to cancer progression and metastatic propensity. The 4T1 tumor is a clinically relevant model of spontaneous breast cancer metastasis. Here we characterize 4T1-derived cell lines for EMT, in vitro invasiveness and in vivo metastatic ability. Contrary to expectations, the 67NR cells, which form primary tumors but fail to metastasize, express vimentin and N-cadherin, but not E-cadherin. 4T1 cells, however, express E-cadherin, are highly migratory and invasive, and metastasize to multiple sites. The 66cl4 metastatic cells display mixed epithelial and mesenchymal markers, but are less migratory and invasive than 67NR cells. These findings demonstrate that the metastatic ability of breast cancer cells does not correlate with genotypic and phenotypic properties of EMT per se, and suggest that other processes may govern metastatic capability. Gene expression analysis also has not identified differences in EMT markers, but has identified several candidate genes that may influence metastatic ability.
Publication Title
Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Photobiomodulation (PBM) with blue light induces a biphasic dose response curve in proliferation of immortalized human keratinocytes (HaCaT), with a maximum anti-proliferative effect reached with 30min (41.4J/cm). The aim of this study was to test the photobiomodulatory effect of 41.4J/cm2 blue light irradiation on ROS production, apoptosis and gene expression at different time points after irradiation of HaCaT cells in vitro. ROS concentration was increased 30min after irradiation. However, already 1h after irradiation, cells were able to reduce ROS and balance the concentration to a normal level. The sudden increase in ROS did not damage the cells, which was demonstrated with FACS analysis where HaCaT cells did not show any sign of apoptosis after blue light irradiation. Furthermore, a time course could be seen in gene expression analysis after blue light, with an early response of stimulated genes already 1h after blue light irradiation, leading to the discovery of the aryl hydrocarbon receptor as possible target for blue light irradiation.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Photobiomodulation (PBM) with blue light induces a biphasic dose response curve in proliferation of immortalized human keratinocytes (HaCaT), with a maximum anti-proliferative effect reached with 30min (41.4J/cm). The aim of this study was to test the photobiomodulatory effect of 41.4J/cm2 blue light irradiation on ROS production, apoptosis and gene expression at different time points after irradiation of HaCaT cells in vitro. ROS concentration was increased 30min after irradiation. However, already 1h after irradiation, cells were able to reduce ROS and balance the concentration to a normal level. The sudden increase in ROS did not damage the cells, which was demonstrated with FACS analysis where HaCaT cells did not show any sign of apoptosis after blue light irradiation. Furthermore, a time course could be seen in gene expression analysis after blue light, with an early response of stimulated genes already 1h after blue light irradiation, leading to the discovery of the aryl hydrocarbon receptor as possible target for blue light irradiation.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Photobiomodulation (PBM) with blue light induces a biphasic dose response curve in proliferation of immortalized human keratinocytes (HaCaT), with a maximum anti-proliferative effect reached with 30min (41.4J/cm). The aim of this study was to test the photobiomodulatory effect of 41.4J/cm2 blue light irradiation on ROS production, apoptosis and gene expression at different time points after irradiation of HaCaT cells in vitro. ROS concentration was increased 30min after irradiation. However, already 1h after irradiation, cells were able to reduce ROS and balance the concentration to a normal level. The sudden increase in ROS did not damage the cells, which was demonstrated with FACS analysis where HaCaT cells did not show any sign of apoptosis after blue light irradiation. Furthermore, a time course could be seen in gene expression analysis after blue light, with an early response of stimulated genes already 1h after blue light irradiation, leading to the discovery of the aryl hydrocarbon receptor as possible target for blue light irradiation.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples