To identify liver transcripts differentially expressed due to treatment with N, N-dimethyl-p-toluidine (DMPT) and p-toluidine, we collected RNA during the from male F344/N rats exposed to 0, 1, 6, 20, 60 or 120 mg/kg DMPT (or p-toluidine), 5 days after exposure for animals 5-6 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip Array.
Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats.
Specimen part
View SamplesOur studies provide direct evidence that O-glycosylation pathways play a role in the regulation of cell growth through apoptosis and proliferation pathways. Eight small molecular weight analogues of the GalNAc-alpha-1-O-serine/threonine structure based on 1-benzyl-2-acetamido-2- deoxy-alpha-O-D-galactopyranoside have been synthesised and tested in 5 human colorectal cancer cell lines. Three inhibitors, 1-benzyl-2-acetamido-2-deoxy-alpha-O-D-galactopyranoside and the corresponding 2-azido- and C-glycoside analogues, were screened in two colorectal cancer cell lines at 0.5mM and showed induction of apoptosis. Proliferation was down regulated in the same two cell lines with all three inhibitors, as detected by Ki67 staining and gene array. Treatment both cell lines with inhibitors led to changes in glycosylation detected with peanut lectin. The competitive action of the inhibitors resulted in the intracellular formation of 28 aryl-glycan products which were identified by MALDI and electrospray mass spectroscopy. The structures found map onto known O-glycosylation biosynthetic pathways and showed a differential pattern for each of the inhibitors in both cell lines. Gene array analysis of the glycogenes illustrated a pattern of glycosytransferases that matched the glycan structures found in glycoproteins and aryl-glycans formed in the PC/AA/C1/SB10C cells, however there was no action of the three inhibitors on glycogene transcript levels. The inhibitors act at both intermediary metabolic and genomic levels, resulting in altered protein glycosylation and arylglycan formation. These events may play a part in growth arrest.
O-glycan inhibitors generate aryl-glycans, induce apoptosis and lead to growth inhibition in colorectal cancer cell lines.
No sample metadata fields
View SamplesTo investigate genes possibly regulated by TTF-1 in small cell lung cancer cell lines, we compared gene expression profiles of NCI-H209 and Lu139 cell lines electroporated with control and TTF-1 siRNAs.
An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.
Cell line
View SamplesThe purpose of the dataset is to analyze expression of genes induced by KRAS and regulated by TBK1
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1.
Specimen part
View Sampleswe report additional phenotypes of mHtt mice that are modified in Pin1 knock-out mice Overall design: RNAs from the striatum of three mice of 12 months of age were purified for each of the genotypes (PinWT/HttWT; PinKO/HttWT; PinWT/HttKI; PinKO/HttKi) to carry out gene expression profiling
Effects of Pin1 Loss in Hdh(Q111) Knock-in Mice.
No sample metadata fields
View SamplesAdipose tissue iNKT cells have different functions than iNKT cells in the blood and other organs.
Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue.
Age, Specimen part
View SamplesWe established and characterized a new recessive mutant mouse line kta41 with a point mutation in Scube3 at position 882. The mutant line was detected by screening for morphological abnormalities in the Munich ENU-mutagenesis program. The mutation was mapped by microsatellite markers to mouse chromosome 17, between markers D17MIT29 and D17MIT101. Candidate gene approaches failed due to the low recombination frequency and the high number of genes within the mapped interval. Whole genome sequencing approaches revealed a C to A transversion on position 882 in Scube3 that leads to a missense mutation in the protein (Asn294Lys). We did a broad phenotypic analysis of the mutant mouse line in the German Mouse Clinic (GMC), and followed up the found alterations by detailed phenotypic characterization. Scube3-kta41-/- mice show a series of phenotypic alterations, mainly in the skeleton, behavior and neurological abnormalities as well as changes in physiology, metabolism and immune status.
The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.
Sex, Age
View SamplesSingle cell sequencing of microglia and perivascular macrophages was performed on brain tissue from different brain regions to obtain single cell expression profiles dependent on celltype and regional location. Overall design: 425 cells from mouse (CD-1) brains at different postnatal ages as well as embryonic day E11.5-E18.5.
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.
Subject
View SamplesMicroglia play critical roles in neural development and homeostasis. They are also implicated in neurodegenerative and neuroinflammatory diseases of the central nervous system (CNS). However, little is known about the presence of spatially and temporally restricted subclasses of microglia during CNS development and disease. Here, we combined massively parallel single-cell analysis, single-molecule FISH, advanced immunohistochemistry and computational modelling to comprehensively characterize novel microglia subclasses, which were transcriptionally different from perivascular macrophages, in up to six different CNS regions during development and diseases. Single-cell analysis revealed specific time- and region-dependent microglia subtypes during homeostasis. In contrast, demyelinating and neurodegenerative diseases evoked context-dependent microglia subtypes with distinct molecular hallmarks and diverse cellular kinetics. Finally, diverse microglia subsets were also identified in normal and diseased human brains. Our data provide new insights into the CNS endogenous immune system during development, health and perturbations. Overall design: CD45+ cells isolated from healthy and MS-affected human brains were FACS-sorted in 384-well plates and used for scRNAseq. The patients were aged between 22 and 25 years. Data comprises 5 healthy and 5 MS patients. CEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016).
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.
Specimen part, Subject
View SamplesThe mitochondrial calcium uniporter has been proposed to coordinate the organelle's energetics with cytosolic calcium signaling. Previous studies have shown that the uniporter current is extremely high in mitochondria from brown adipose tissue (BAT), yet the contribution of the uniporter to BAT physiology in vivo is not known. Here, we report the generation and characterization of a mouse model lacking Mcu, the pore forming subunit of the uniporter, specifically in BAT (BAT-Mcu-KO). BAT-Mcu-KO mice are born in Mendelian ratios on a C57BL6/J genetic background, without any overt phenotypes. Although uniporter based calcium uptake is selectively ablated in BAT mitochondria, these mice are able to defend their body temperature in response to cold challenge and exhibit a normal body weight trajectory on a high fat diet. BAT transcriptional profiles at baseline and following cold-challenge are intact and not impacted by loss of Mcu. Unexpectedly, we found that cold powerfully activates the ATF4-dependent integrated stress response in BAT, and increases both circulating FGF21 and GDF15 levels, raising the hypothesis that the integrated stress response partly underlies the pleiotropic effects of BAT on systemic metabolism. Our study demonstrates that the uniporter is largely dispensable for BAT thermogenesis, and unexpectedly, uncovers a striking activation of the integrated stress response of BAT to cold challenge. Overall design: RNA-seq was performed on BAT RNA isolated from BAT-Mcu-KO and control animals housed for 6 hours at 4C or room temp (RT). Samples include 6 control animals at RT; 5 control animals at 4C; 6 BAT-Mcu-KO animals at RT; and 6 BAT-Mcu-KO animals at 4C.
Exploring the In Vivo Role of the Mitochondrial Calcium Uniporter in Brown Fat Bioenergetics.
Sex, Specimen part, Cell line, Subject
View Samples