The transcriptome is the complete set of all RNA transcripts produced by the genome in a cell and reflects the genes that are being actively expressed. Transcriptome analysis is essential for understanding the genetic mechanism controlling the phenotype of a cell.
Characterization of transcriptomes of cochlear inner and outer hair cells.
Specimen part
View SamplesIL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation. Overall design: We carried out high troughput RNA sequencing of RNA isolated from IL-10 producing Foxp3- CD4+ T-cells, which were isolated from the spleen of mice treated with anti-CD3 antibody.
Molecular and functional heterogeneity of IL-10-producing CD4<sup>+</sup> T cells.
Subject
View SamplesCre recombinase-mediated conditional knockout of floxed Dicer1 alleles causes depletion of small RNAs including microRNAs, which function to repress target mRNA expression by inhibiting translation and/or stimulating mRNA degradation.
MicroRNA-183 family expression in hair cell development and requirement of microRNAs for hair cell maintenance and survival.
Specimen part
View SamplesTransgenic FVB/NCrl-Tg(GFAP-Mir183,Mir96,Mir182)MDW1 mice (Tg1MDW) overexpress this neurosensory-specific miRNA cluster in the inner ear and were developed as a model system to identify target genes and biologic processes regulated by the miR-183 cluster.
A mouse model of miR-96, miR-182 and miR-183 misexpression implicates miRNAs in cochlear cell fate and homeostasis.
Specimen part
View SamplesThe p53-regulated long non-coding RNA, lincRNA-p21, has been proposed to promote apoptosis and to repress in trans the expression of genes in the p53 transcriptional network. Here, we report the generation of a conditional knockout mouse model developed to further examine lincRNA-p21 function. Using this genetic approach, we find that the primary function of lincRNA-p21 is to activate in cis the expression of its neighboring gene, the cyclin-dependent kinase inhibitor p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent transcription of p21. Additional phenotypes of lincRNA-p21 deficiency, including deregulated expression and altered chromatin state of a set of Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency could be attributed to diminished p21 levels. This study reveals a novel paradigm, whereby the long non-coding RNA lincRNA-p21 affects global gene expression and influences events in the p53 tumor suppressor pathway by acting in cis as a locus-restricted transcriptional co-activator for p53-mediated expression of p21. Overall design: mRNAseq in 2 cell types (WT and lincRNA-p21 KO) in the presence and absence of Doxorubicin performed in biological triplicate.
LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint.
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View SamplesWe tested how complete or partial loss of endophilin A1, A2 and A3 affects gene expression in mouse hippocampus. Total loss of endophilin (triple knock-outs, TKO) was assessed in newborn mice, since the TKO mice only survive only several hours after birth. Partial loss of endophilin (endoA1,A2 double knock-out, DKO) was assessed between Overall design: 2-3 weeks of age (p13-21).
Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System.
Subject
View SamplesThe overall aim of this experiment was to identify specific genes and molecular pathways regulated by ML290, a small molecule agonist of the relaxin receptor, RXFP1, in the context of liver fibrosis. Overall design: Whole transcriptome mRNA sequencing of transformed LX-2 cells using HiSeq platforms with paired-end 150 bp (PE 150) sequencing strategy, with four biological replicates in each treatment group.
Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.
Specimen part, Cell line, Subject
View SamplesGPR146 is a susceptible gene associated with plasma cholesterol levels in humans, its physiological and molecular functions have not been fully characherized. In this study, we generated Gpr146 whole-body knockout mice and found that depletion of GPR146 led to substantilly reduced plasma total cholesterol levels.
GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis.
Specimen part
View SamplesComparison of CLL and MCL primary cells obtained from a patient with MCL variant Richter syndrome
Mantle cell lymphoma-variant Richter syndrome: Detailed molecular-cytogenetic and backtracking analysis reveals slow evolution of a pre-MCL clone in parallel with CLL over several years.
Specimen part, Disease, Disease stage
View SamplesFinding the differences in gene expression in three regions of the brain, basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV infected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients.
The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment.
Sex, Age, Specimen part, Race
View Samples