Insulin like growth factor 1 (IGF-1) has a central role in mammalian hearing and hearing loss. The auditory and vestibular systems form the inner ear and have a common developmental origin. During chicken early development IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system.
Comparative gene expression study of the vestibular organ of the Igf1 deficient mouse using whole-transcript arrays.
Specimen part
View SamplesHuman embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P.
Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation, and pluripotency in human embryonic stem cells.
No sample metadata fields
View SamplesAn increasing amount of evidence suggests that the small intestine may play an important role in the development of metabolic diseases, such as obesity and insulin resistance. The small intestine provides the first barrier between diet and the body. As a result, dysregulation of biological processes and secretion of signal molecules from the small intestine may be of importance in the regulation and dysregulation of whole body metabolic homeostasis. Changes in gene expression of genes involved in lipid metabolism, cell cycle and immune response may contribute to the aetiology of diet-induced obesity and insulin resistance. In the current study we present a detailed investigation on the effects a chow diet, low fat diet and high fat diet on gene expression along the proximal-to-distal axis of the murine small intestine. The reported results provide a knowledge base for upcoming studies on the role of the small intestine in the aetiology of diet-induced diseases.
Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.
Sex, Specimen part
View SamplesGliogenesis in the Drosophila CNS occurs during embryogenesis and also during the postembryonic larval stages. Several glial subtypes are generated in the postembryonic CNS through the proliferation of differentiated glial cells. The genes and molecular pathways that regulate glial proliferation in the postembryonic CNS are poorly understood. In this study we aimed to use gene expressing profiling of CNS tissue enriched in glia to identify genes expressed in glial cells in the postembryonic CNS.
Glial enriched gene expression profiling identifies novel factors regulating the proliferation of specific glial subtypes in the Drosophila brain.
Specimen part
View SamplesEnhanced secondary Ab responses are a vital component of adaptive immunity, yet little is understood about the intrinsic and extrinsic regulators of nave and memory B cells that results in differences in their responses to Ag. Microarray analysis, together with surface and intracellular phenotyping, revealed that memory B cells have increased expression of members of the TNF receptor, SLAM, B7 and Bcl2 families, as well as the TLR-related molecule CD180 (RP105). Accordingly, memory B cells exhibited enhanced survival, proliferation and Ig secretion, as well as entered division more rapidly than nave B cells in response to both T-dependent and T-independent stimuli. Furthermore, both IgM and isotype switched memory B cells, but not nave B cells, co-stimulated CD4+ T cells in vitro through a mechanism dependent on their constitutive expression of CD80 and CD86. This study demonstrates that upregulation of genes involved in activation, co-stimulation and survival provides memory B cells with a unique ability to produce enhanced immune responses and contributes to the maintenance of the memory B cell pool.
Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells.
Specimen part
View SamplesCells were isolated from healthy human donors (n=2). Unstimulated cells. Cells were stained with CD4, CD45RA, CCR7 and CXCR7. Using flow cytometry, 4 CD4+ T cell populations were sorted: (1) Nave (CD45RA+CCR7+CXCR5-), (2) Central memory (CD45RA-CCR7+CXCR5-), (3) Effector memory (CD45RA-CCR7-CXCR5-) and (4) CXCR5+ cells (CD45RA-CCR7-CXCR5+)
CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses.
Specimen part
View SamplesThe accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR) which is characterised in part by the transcriptional induction of genes involved in assisting protein folding. Translational responses to ER stress have been less well described and here we report on a genome-wide analysis of translational regulation in the response to the ER stress-inducing agent dithiothreitol (DTT) in Saccharomyces cerevisiae. Although the observed polysome profiles were similar under control and ER stress conditions microarray analysis identified transcipt-specific translational regulation. Genes with functions in ribosomal biogenesis and assembly were translationally repressed under ER stress. In contrast mRNAs for known UPR genes, including the UPR transcription factor HAC1, the ER-oxidoreductase ERO1 and the ER-associated protein degradation (ERAD) gene DER1 were enriched in polysomal fractions under ER stress conditions. In addition, we show that splicing of HAC1 mRNA is required for efficient ribosomal loading and that Gcn2p is required for normal HAC1 splicing, so shedding light on the role of this protein kinase in the UPR pathway.
Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel genes associated with lymph node metastasis in triple negative breast cancer.
Specimen part, Disease stage, Subject
View SamplesThe contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.
Differential Effects of the Hormonal and Copper Intrauterine Device on the Endometrial Transcriptome.
Age, Specimen part
View SamplesTriple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis. It is characterised by the absence of hormone receptors for estrogen, progesterone, and human epidermal growth factor 2, and as a consequence there are no targeted endocrine treatments available. TNBC patients are more likely to develop metastases and disease relapse than patients with other breast cancer subtypes. The identification of biomarkers that can be used to predict which patient is likely to develop metastatic disease remains a priority since this is the major cause of cancer-related death in these women.
Novel genes associated with lymph node metastasis in triple negative breast cancer.
Specimen part
View Samples