CNIs drastically modify the Treg specific transcriptional program in vivo in an IL-2 dependent manner
IL-2 therapy restores regulatory T-cell dysfunction induced by calcineurin inhibitors.
Specimen part, Treatment
View SamplesCalcific aortic valvular disease (CAVD) is characterized by sclerosis of the aortic valve leaflets and recent clinical studies have linked several other risk factors to this disease, including male sex. In this study we examined potential sex-related differences in gene expression profiles between porcine male and female valvular interstitial cells (VICs) to explore possible differences in CAVD propensity on the cellular level.
Sex-related differences in gene expression by porcine aortic valvular interstitial cells.
Sex, Specimen part
View SamplesBackground & Aims: MiRNAs are small (~22 nucleotide), non-coding RNA molecules that regulate gene expression through imperfect complementarity with target messenger RNAs. The function of miRNA in mammalian organogenesis is largely unknown. Conditional loss-of-function of Dicer, the enzyme that processes precursor miRNA transcripts into their mature, active form, has been shown to cause severe defects in a number of organ systems. Here we address the role of Dicer in liver development and function. Methods: Mice lacking Dicer function in hepatocytes were generated using an Afp-Cre strain to drive deletion of a floxed Dicer allele. Deletion of the flox-dicer allele was confirmed by quantitative PCR. Decreased miRNA levels detected by quantitative RT-PCR and in situ hybridization confirmed loss of Dicer function. Gene expression microarray analysis was performed on liver RNA from P28 mutant and control mice. Liver sections from mutant and control mice ranging from embryonic stages through 3-4 months of age were examined and liver function tests were performed on adult mice. Results: Mice lacking hepatocyte Dicer function were born alive at the expected frequency, and had grossly normal appearance and behavior. Despite the loss of mature miRNA, hepatic function was normal, as reflected by normal blood gludose, albumin, cholesterol, and bilirubin. However, mutant mice between 2-4 months of age exhibit progressive hepatocyte damage, elevated ALT/AST, with evidence of balanced proliferation and apoptosis in the lobule. Microarray analysis indicates large-scale changes in gene expression, with increased expression of many miRNA targets, as well as imprinted genes. Conclusions: Loss of miRNA processing in the liver at late gestation has a remarkably mild phenotype, suggesting that miRNAs do not play an essential role in hepatic physiology. However, miRNA deficiency results in hepatocyte apoptosis and balanced hepatocyte regeneration. Finally, microarray analysis of gene expression in mutant liver suggests a previously unrecognized role for Dicer in the repression of imprinted genes.
Hepatic function is preserved in the absence of mature microRNAs.
Age, Specimen part
View SamplesThe goal was to identify genes targeted by miR-30a.
The microRNA-30 family is required for vertebrate hepatobiliary development.
No sample metadata fields
View SamplesAdult BALB/c female mice were injected intraperitoneally with a single dose at 20 mg per kg of antisense oligonucleotide either against miR-29a (5-TAACCGATTTCAGATGGTGCTA-3) or against a scrambled sequence (5-TCATTGGCATGTACCATGCAGCT-3 Antisense oligonucleotides contained 2-O-methoxyethyl (2-MOE), 2-flouro (2-F) 2'-alpha-flouro units with a phosphorothioate backbone (Regulus Therapeutics). Six days following the injection, liver was isolated, total RNA was prepared as described above, and the RNA was amplified and biotinylated using the MessageAmp Premier kit (Ambion). Samples (n=4 each experimental and control) were hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 Arrays in the Childrens Hospital of Philadelphia Nucleic Acids Core Facilityand analyzed with the assistance of the Penn Bioinformatics Core. Probe intensities were normalized using the GCRMA method and the significance of the log2-transformed, GCRMA-normalized signal intensities was determined using SAM
MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experimental biliary atresia.
Sex, Specimen part, Treatment
View SamplesIn this study, we explored x-inactivation in monkey embryos (ICM and TE separately) and pluripotent stem cells (IVF derived ES, SCNT-derived ES and monkey iPS)
X-chromosome inactivation in monkey embryos and pluripotent stem cells.
Sex, Specimen part
View SamplesA unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state. Although quiescence serves an essential role in preserving stem cell function until the stem cell is needed in tissue homeostasis or repair, defects in quiescence can lead to an impairment in tissue function, the extent to which stem cells can regulate quiescence is unknown. Here, we show that the stem cell quiescent state is composed of two distinct functional phases: G0 and an alert phase we term GAlert, and that stem cells actively and reversibly transition between these phases in response to injury-induced, systemic signals. Using genetic models specific to muscle stem cells (or satellite cells (SCs)), we show that mTORC1 activity is necessary and sufficient for the transition of SCs from G0 into GAlert and that signaling through the HGF receptor, cMet is also necessary. We also identify G0-to-GAlert transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into GAlert possess enhanced tissue regenerative function. We propose that the transition of quiescent stem cells into GAlert functions as an 'alerting' mechanism, a novel adaptive response that positions stem cells to respond rapidly under conditions of injury and stress without requiring cell cycle entry or a cell fate commitment.
mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert).
Specimen part, Treatment, Time
View SamplesCarbon nanotubes are cylindrically-shaped carbon nanostructures, made up of layers of graphene rolled onto themselves, with diameters similar to those of neuronal processes. In the last decade, CNT have been used as biocompatible growing substrates for neuronal attachment, differentiation and growth. In the perspective of new developments in tissue engineering, and in particular in spinal cord repair strategies, based on the use of CNTs, our aim is to clarify the biophysical interactions between CNTs and spinal cord neurons, studying the development of the morphological and functional characteristics of spinal neurons grown on CNT-based interfaces.
Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.
Specimen part
View SamplesPulmonary alveoli are complex architectural units thought to undergo endogenous or pharmacologically induced programs of regeneration and degeneration. To study the molecular mechanism of alveoli loss mice were calorie restricted at different timepoints. Lungs were harvested and processed for RNA extraction.
Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression.
Time
View SamplesIt has been shown that dexamethasone (Dex) impairs the normal lung septation that occurs in the early postnatal period. Treatment with retinoic acid (ATRA) abrogates the effects of Dex. To understand the molecular basis for the Dex indiced inhibition of the formation of the alveoli and the ability of ATRA to prevent the inhibition of septation, gene expression was analyzed in 4-day old mice treated with diluent (control), Dex-treated and ATRA+Dex-treated.
DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.
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