Retinoblastoma gene (Rb1) is required for proper cell cycle exit in the developing mouse inner ear and its deletion in the embryo leads to proliferation of sensory progenitor cells that differentiate into hair cells and supporting cells. In the Pou4f3-Cre:Rb1 flox/flox (Rb1 cKO) inner ear, utricular hair cells differentiate and survive into adulthood whereas differentiation and survival of cochlear hair cells are impaired. To comprehensively survey the pRb pathway in the mammalian inner ear, we performed microarray analysis of Rb1 cKO cochlea and utricle.
Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs.
Age, Specimen part
View SamplesThe goal of this study was to compare the transcriptional profile (RNA-seq) of imbibed Arabidopsis thaliana Columbia-0 ecotype seeds that were treated with a 20 min red or far red pulse. The red-light pulse induces germination. Overall design: Col-0 seeds were sown in clear plastic boxes, each containing 10 mL of 0.8 % (w/v) agar in demineralized water. To establish a minimum and equal photo-equilibrium, seeds were imbibed for 2 hours in darkness and then irradiated for 20 min with a saturated far-red pulse (FRp, calculated Pfr/P= 0.03, 42 µmol.m-2.s-1) in order to minimize the quantities of Pfr formed during their development in the mother plant. Seeds were then stratified at 5 °C in darkness for 3 days, prior to the 20 minutes with a saturated red pulse (Rp, calculated Pfr/P= 0.87, 0.05 µmol.m-2.s-1) or FRp. Three biological replicates of each condition were collected 12 hours after the corresponding R and FR light pulses.
Alternative Splicing Regulation During Light-Induced Germination of <i>Arabidopsis thaliana</i> Seeds.
Subject
View SamplesIn chick basilar papilla, hair cells can be regenerated after gentamicin treatment. To identify genes and pathways involved in this process, we performed microarray analysis on the basilar papilla 0, 48 and 72 hours after gentamicin.
Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration.
Specimen part
View SamplesStudy on differential gene expression and splicing between wildtype and clock mutants. This study is part of a comparative analysis of the role of Protein Methyltransferase 5 in the regulation of transcriptional and post-transcriptional processes simultaneously in Arabidopsis and Drosophila.
A methyl transferase links the circadian clock to the regulation of alternative splicing.
Specimen part
View SamplesNotch1 signaling is absolutely essential for steady-state thymic lymphopoiesis, but the role of other Notch receptors, and their potential overlap with the function of Notch1, remains unclear. Here we show that like Notch1, Notch3 is differentially expressed by progenitor thymocytes, peaking at the DN3 progenitor stage. Using mice carrying a gene-trapped allele, we show that thymic cellularity is slightly reduced in the absence of Notch3, although progression through the defined sequence of TCR- development is normal, as are NKT and TCR cell production.
Nonoverlapping functions for Notch1 and Notch3 during murine steady-state thymic lymphopoiesis.
Sex, Age, Specimen part
View SamplesExercise attenuates the development of chronic non-communicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed using a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for Metabolism (38 gene sets), Cell Cycle (36 gene sets), Disease (27 gene sets), Gene Expression and Transcription (22 gene sets), Organelle Biogenesis (4 gene sets), Cellular Response to Stimuli (8 gene sets), Immune System (8 gene sets), Vesicle Mediated Transport (4 gene sets), and Transport of Small Molecules (3 gene sets). Specific gene expression included: Oxidative catabolism of glucose including PDHB (p<0.001), PDHX (p<0.001), MPC1 (p<0.009), and MPC2 (p<0.007); Oxidative phosphorylation genes including SDHA (p<0.006), SDHB (p<0.001), NDUFB1 (p<0.002), NDUFA2 (p<0.001); Transcription Genes including PGC1α (p<0.030) and PRKAB2 (p<0.011); Hypertrophy gene MSTN (p<0.001); and the Myokine generating FNDC5 gene (p<0.008). Long-term electrically induced exercise de-methylated the major transcription factor, PGC1a. Taken together, these findings support that long term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.
Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury.
Sex, Specimen part, Disease
View SamplesInteraction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them.
Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation.
Specimen part
View SamplesWe used a novel approach to study the acute effect of three physiologic stressors (active contractions, vibration, and systemic heat stress) in human skeletal muscle. Three hours after the completion of a dose of physiologic stress, we sampled the soleus (contraction and vibration) or vastus lateralis (heat) muscle and developed a unique gene expression signature for each stressor. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold change), PGC-1 (5.46 fold change), and ABRA (5.98 fold change); and repressed MSTN (0.56 fold change). Heat stress repressed PGC-1 (0.74 fold change); while vibration induced FOXK2 (2.36 fold change). Vibration similarly caused a down regulation of MSTN (0.74 fold change), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 while heat stress repressed PGC-1 (0.74 fold change) and ANKRD1 genes (0.51 fold change). These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.
Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.
Sex, Specimen part
View SamplesDifferential expression was used to access gene differences after Entamoeba histolytica infection.
The expression of REG 1A and REG 1B is increased during acute amebic colitis.
Specimen part
View SamplesHistone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (E). Here, we report that the E-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of E-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Specimen part
View Samples