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SRP160902
Mus musculus
112 Downloadable Samples
Illumina HiSeq 4000
Description
Sensitivity to different pain modalities has a genetic basis that remains largely unknown. The use of closely related inbred mouse strains can facilitate gene mapping of nociceptive behaviors in preclinical pain models. We previously reported enhanced sensitivity to acute thermal nociception in C57BL/6J (B6J) versus C57BL/6N (B6N) substrains. Here, we expanded on pain phenotypes and observed an increase in inflammatory nociceptive behaviors induced by hindpaw formalin injections in B6J versus B6N mice (Charles River Laboratories). No strain differences were observed in mechanical or thermal hypersensitivity or in paw diameter following the Complete Freund s Adjuvant (CFA) model of inflammatory pain, indicating specificity in the inflammatory nociceptive stimulus. In the chronic nerve constriction injury (CCI), a model of neuropathic pain, no strain differences were observed in baseline mechanical threshold or in mechanical hypersensitivity up to one month post-CCI. We replicated the enhanced thermal nociception in B6J mice in the 52.5 C hot plate test relative to B6N mice from The Jackson Laboratory. Using a B6J x B6N-F2 cross (N=164), we mapped a major QTL underlying hot plate sensitivity to chromosome 7 that peaked at 26 Mb (LOD = 3.81, 8.74 Mb-36.50 Mb) that was more pronounced in males. Genes containing expression QTLs (eQTLs) associated with the peak nociceptive marker that have been implicated in pain and inflammation include Ryr1, Cyp2a5, Pou2f2, Clip3, Sirt2, Actn4, and Ltbp4 (FDR < 0.05). Future studies involving positional cloning and gene editing will determine the quantitative trait gene(s) and potential pleiotropy of this locus across other pain modalities. RNA-seq data and genotype information from striatum punches of F2 C57BL/6J (B6J) cross C57BL/NJ (B6NJ) oxycodone-treated mice. Genotypes are given relative to B6J allele, eg 0 = homozygous B6J. Overall design: C57BL/6J (B6J) and C57BL/NJ (B6NJ) mice were purchased from JAX at 7 weeks of age and were habituated in the vivarium one week prior to experimental testing that occurred next door. B6J females were crossed to B6NJ males to generate B6J x B6NJ-F1 mice and B6J x B6NJ F1 offspring were intercrossed to generate B6J x B6NJ F2 mice. Mice were 50-100 days old at the time of testing. F2 mice recieved four daily oxycodone injections (20 mg/kg, i.p.). Ninety SNP markers spaced approximately 30 Mb (approximately 15 cM) apart were genotyped using a custom-designed Fluidigm array.
Publication Title
C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 50 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia a prominent symptom of chronic pain.
Publication Title
The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Skeletal muscle adapts to resistance exercise (RE) performance acutely and chronically. An important regulatory step of muscle adaptation to RE is gene expression. Microarray analysis can be used as an exploratory method to investigate how genes and gene clusters are modulated acutely and chronically by RE. The purpose of the present study was to investigate the effect of training status in the basal (rested) and pre- to 24h post-RE on the global transcriptome in vastus lateralis muscle biopsies of young men. Muscle biopsies of nine young men who undertook RE training for 10-wks were collected pre and 24h post-RE at the first (W1) and last (W10) weeks of training and analysed using microarray. An unaccustomed RE bout (at W1) up-regulated muscle gene transcripts related to stress (e.g., heat shock proteins), damage and inflammation, structural remodelling, protein turnover and increased translational capacity. Trained muscles (at W10) became more efficient metabolically, as training favoured a more oxidative metabolism, refined response to stress, showed by genes suppression related to RE-induced stress and inflammation, and up-regulated genes indicating greater muscle contractile efficiency and contribution to promote muscle growth and development. These data highlight that chronic repetition of RE increases muscle efficiency and adapt muscles to respond more specifically and accurately to RE-induced stress.
Publication Title
Resistance training in young men induces muscle transcriptome-wide changes associated with muscle structure and metabolism refining the response to exercise-induced stress.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Telogen (resting phase) hair follicles are more radioresistant than anagen (growth phase) ones. Irradiation of BALB/c mice in the anagen phase with -rays at 6 Gy induced hair follicle dystrophy, whereas irradiation in the telogen phase induced the arrest of hair follicle elongation without any dystrophy after post-irradiation depilation. In contrast, FGF18 was highly expressed in the telogen hair follicles to maintain the telogen phase and also the quiescence of hair follicle stem cells. Therefore, the inhibition of FGF receptor signaling at telogen induced the dystrophy after post-irradiation depilation. In addition, the administration of recombinant FGF18 suppressed cell proliferation in the hair follicles and enhanced the repair of radiation-induced DNA damage, so FGF18 protected the anagen hair follicles against radiation damage to enhance hair regeneration. Moreover, FGF18 reduced the expression of cyclin B1 and cdc2 in the skin and FGF18 signaling induced G2/M arrest in the keratinocyte cell line HaCaT, although no obvious change of the expression of DNA repair genes was detected by DNA microarray analysis. These findings suggest that FGF18 signaling for the hair cycle resting phase causes radioresistance in telogen hair follicles by arresting the proliferation of hair follicle cells.
Publication Title
FGF18 signaling in the hair cycle resting phase determines radioresistance of hair follicles by arresting hair cycling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Although various mechanisms have been inferred for combinatorial actions of multiple carcinogens, these mechanisms have not been well demonstrated in experimental carcinogenesis models. We evaluated mammary carcinogenesis initiated by combined exposure to various doses of radiation and chemical carcinogens. Female rats at 7 weeks of age were -irradiated (0.22 Gy) and/or exposed to 1-methyl-1-nitrosourea (20 or 40 mg/kg, single intraperitoneal injection) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (40 mg/kg/day by gavage for 10 days) and were observed until 50 weeks of age. The incidence of mammary carcinoma increased steadily as a function of radiation dose in the absence of chemicals; mathematical analysis supported an additive increase when radiation was combined with a chemical carcinogen, irrespective of the chemical species and its dose. Hras mutations were characteristic of carcinomas that developed after chemical carcinogen treatments and were overrepresented in carcinomas induced by the combination of radiation and MNU (but not PhIP), indicating an interaction of radiation and MNU at the level of initiation. The expression profiles of seven classifier genes, previously shown to distinguish two classes of rat mammary carcinomas, categorized almost all examined carcinomas that developed after individual or combined treatments with radiation (1 Gy) and chemicals as belonging to a single class; more comprehensive screening using microarrays and a separate test sample set failed to identify differences in gene expression profiles among these carcinomas. These results suggest that a complex, multilevel interaction underlies the combinatorial action of radiation and chemical carcinogens in the experimental model.
Publication Title
Molecular characterization of cancer reveals interactions between ionizing radiation and chemicals on rat mammary carcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We have found that the cell yield of oligodendrocyte precursor cells (OPCs) are higher in 31.5 than in 37 not by suppression of apoptosis but by enhancement of proliferation.
Publication Title
Hypothermia-induced increase of oligodendrocyte precursor cells: Possible involvement of plasmalemmal voltage-dependent anion channel 1.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The goal of this study was to investigate the role of intragenic CTCF in alternative pre-mRNA splicing through a combined CTCF-ChIP-seq and RNA-seq approach. CTCF depletion led to decreased inclusion of weak upstream exons. Overall design: CTCF ChIP-seq was performed in BJAB and BL41 B cell lines and normalized relative to Rabbit Ig control IP-seq reads. RNA-seq was performed in BJAB and BL41 cells transduced with shRNA against CTCF or RFP as a control, and in untransduced cells as well.
Publication Title
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 163 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Gene expression profiling based classification of DLBCL patients versus healthy donors provides insights on transcriptional regulation processes.
Publication Title
T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Ion Torrent Proton
Description
We found that a small molecule inhibitor of PRMT4 inhibited cell growth of a subset of multiple myeloma cell lines. To identify biomarkers that predict the sensitivity of myeloma cells to PRMT4 inhibition, we performed transcriptomic analysis of multiple myeloma cell lines. Overall design: Amplicon sequencing of thirteen multiple myeloma cell lines was performed on the Ion Torrent platform. Steady-state gene expression profile of sensitive cells were compaired with that of insensitive cells.
Publication Title
TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Alternative splicing (AS) is a post-transcriptional gene regulatory mechanism that contributes to proteome diversity. Aberrant splicing mechanisms (mutations, polymorphisms, insertion/deletion etc.) contribute to various cancers and muscle related conditions such as Duchenne muscular dystrophy. However, dysregulation of AS in Cancer Cachexia (CC) patients remains unexplored. Our objectives were (i) to profile alternatively spliced genes (ASGs) on a genome-wide scale, and (ii) to identify DE alternatively spliced genes (DASGs) associated with CC. Rectus abdominis muscle biopsies obtained from cancer patients were stratified into cachectic cases (n=21, classified based on International consensus diagnostic framework for CC) and non-cachectic controls (n=19, weight stable cancer patients). Human Transcriptome array 2.0 was used for profiling ASGs using the total RNA isolated from muscle biopsies. Representative DASG signatures were validated using semi-quantitative RT-PCR. We identified 8960 ASGs, of which 922 DASGs (772 up-regulated, 150 down-regulated) were identified at > 1.4 fold-change and p < 0.05. Representative DASGs when validated by semi-quantitative RT-PCR also showed similar trends, confirming the primary findings from the genome-wide arrays. Identified DASGs were associated with myogenesis, adipogenesis, protein ubiquitination and inflammation. Up to 10% of the DASGs exhibited cassette exon (exon included or skipped) as a predominant form of AS event. We also observed other forms of AS events such as intron retention, alternate promoters. Overall, we have, for the first time conducted global profiling of muscle tissue to identify DASGs associated with CC. The mechanistic roles of the identified DASGs in CC pathophysiology using model systems is warranted, as well as replication of findings in independent cohorts.
Publication Title
Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia.
Sample Metadata Fields
Specimen part
View Samples