Background: Transcriptome variability is due to genetic and environmental causes, much like any other complex phenotype. Ascertaining the transcriptome differences between individuals is an important step to understand how selection and genetic drift may affect gene expression. To that end, extant divergent livestock breeds offer an ideal genetic material.
Impact of breed and sex on porcine endocrine transcriptome: a bayesian biometrical analysis.
Sex, Specimen part
View SamplesGene expression analysis of hypothalami from female animals at different juvenile developmental reproductive stages. Results provide insight into the role of the hypothalamus in controlling the onset of puberty. Overall design: SD rats were housed (8/cage) in a controlled environment and euthanized at different ages (PND=7, PND=14, Early Juvenile: 21 days, Late Juvenile: 28 days, Late Proestus (the day of first ovulation): 30-33 days. Rats were anesthetized and brains were rapidly removed. The medial basal hypothalamus (MBH) was dissected away from the rest of the brain and flash frozen. Total RNA was isolated from each sample using Qiagen''s RNeasy Mini Kit (Valencia, CA). Samples were bioanalyzed on a RNA 6000 Nano chip kit to check for integrity and concentration before sending it to OHSU''s Massively Parallel Sequencing Shared Resource for library preparation and sequencing.
Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty.
No sample metadata fields
View SamplesHypothalamic hamartomas (HHs) are congenital lesions of the neuroendocrine brain composed of neurons and astroglia. Frequently, HHs are associated with central precocious puberty (CPP) and/or gelastic seizures. Because HHs might express genes similar to those required for the initiation of normal puberty we used cDNA arrays to compare the gene expression profile of a HH associated with CPP with three HHs not accompanied by sexual precocity. Our aim was to identify genes whose expression may be selectively altered in the HH with CPP and hence, involved in the onset of puberty.
Gene expression profiling of hypothalamic hamartomas: a search for genes associated with central precocious puberty.
No sample metadata fields
View SamplesArtificial selection has resulted in animal breeds with extreme phenotypes. As an organism is made up of many different tissues and organs, each with its own genetic programme, it is pertinent to ask what are the relative contributions of breed or sex when assessed across tissues.
Transcriptome architecture across tissues in the pig.
Age
View SamplesCutaneous squamous tumors rely on autocrine/paracrine loops for proper fitness. Targeting this Achilles heel is therefore considered a potential avenue for patient treatment. However, the mechanisms that engage and sustain such programs during tumor ontogeny are poorly understood. Here, we show that two Rho/Rac activators, the exchange factors Vav2 and Vav3, control the expression of an epithelial autocrine/paracrine program that regulates keratinocyte survival and proliferation as well as the creation of an inflammatory microenvironment. Vav proteins are also critically involved in some of the subsequent autocrine signaling loops activated in keratinocytes. The genetic inactivation of both Vav proteins reduces tumor multiplicity without hampering skin homeostasis, thus suggesting that pan-specific Vav therapies may be useful in skin tumor prevention and treatment.
The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
Specimen part
View SamplesRett syndrome (RTT, OMIM #312750) is a severe X-linked neurodevelopmental disorder linked to heterozygous de novo mutations in the MECP2 gene. MECP2 encodes methyl-CpG-binding protein 2 (MeCP2), which represses gene transcription by binding to 5-methylcytosine residues in symmetrically positioned CpG dinucleotides. The disorder is almost exclusively diagnosed in females, because males affected by the disease usually die perinatally due to severe encephalopathy. Direct MeCP2 target genes underlying the neuropathogenesis of RTT remain largely unknown.
FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice.
No sample metadata fields
View SamplesRenal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell RCC (nccRCC) that have no standard therapy. The oncogenic drivers in these tumors are unknown. We performed a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, Single Nucleotide Polymorphism array, fluorescence in-situ hybridization, immunohistochemistry, and cell-based assays. We identified recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%), and MTOR (8%). Integrated analysis revealed distinct molecular subsets, including a subset of 26% uRCC characterized by NF2-loss, dysregulated Hippo-YAP pathway and worse survival. Overall design: Analysis of RNA from uRCC with or without NF2-loss
Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets.
Specimen part, Subject
View SamplesDiabetic foot ulcers (DFUs) are the leading cause of lower leg amputations in diabetic population. To better understand molecular pathophysiology of DFUs we used patients specimens and genomic profiling. We identified 3900 genes specifically regulated in DFUs. Moreover, we compared DFU to human skin acute wound (AW) profiles and found DNA repair mechanisms and regulation of gene expression among the processes specifically suppressed in DFUs, whereas essential wound healing-related processes, inflammatory/immune response or cell migration, were not activated properly. To identify potential regulators of DFU-specific genes, we used upstream target analysis. We found miR-15/16 family enriched in DFUs, but not in AW, which was confirmed by qPCR. We found that infection with the most common DFU colonizer, Staphylococcus aureus, triggers induction of miR-15-5p, which in turn, targets multiple DFU-specific genes, including genes involved in DNA repair (WEE1, MSH2 and RAD50) and the regulator of inflammatory pathway, IKBKB. Induction of miR-15b-5p, either by miR-mimic transfection in vitro or by S. aureus infection of acute wounds ex vivo, suppressed both WEE1 and IKBKB. Consequently, we detected an increase in DNA double strand breaks in DFUs. In summary, our data indicate that S. aureus infection, via induction of miR-15b-5p, may lead to suppression of DNA repair mechanisms and a sub-optimal inflammatory response, contributing to pathophysiology of DFU patients
Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers.
Specimen part, Disease, Disease stage
View SamplesVascular smooth muscle cells (VSMCs) respond to biomechanical stretch with specific changes in gene expression which govern the phenotype of these cells. The mechanotransducer zyxin is a
Loss of the mechanotransducer zyxin promotes a synthetic phenotype of vascular smooth muscle cells.
Specimen part, Treatment
View SamplesPurpose:To take a comprehensive effort in characterizing the brain vasculature gene expression upon hyperglycemia. Methods: We extracted mRNA from brain microvasculature fragments isolated from a genetic mouse model of hyperglycemia (Ins2-AKITA) and WT mice and analyzed their transcriptome with RNA sequencing The samples were sequenced on an Illumina HiSeq 2500 sequencer at the SNP&SEQ sequencing facility (Science for Life laboratory (SciLifeLab), Uppsala sequencing node). The reads were aligned to the Ensembl mouse gene assembly (NCBIM37) using Tophat2 software (version 2.0.4). The duplicated reads were removed using the picard tool (version 1.92). To identify the genes significantly enriched in the pericyte samples as compared with microvascular samples, statistical tests were performed using the Cufflinks tool (version 2.2.1) Results: Twenty-three genes were significantly regulated in mutant when compared to WT (False Discovery Rate < 0.05) Overall design: The microvascular RNA from two male heterozygous Ins2-AKITA mice and three littermate wild-type controls were processed and sequenced on the Illumina HiSeq 2500 platform in the sequencing facility in Uppsala University.
Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier.
Sex, Specimen part, Subject
View Samples