The initial segment of the epididymis is vital for male fertility, therefore, it is important to understand the mechanisms that regulate this important region. Deprival of testicular luminal fluid factors/lumicrine factors from epididymis, a subset of cells within the initial segment undergo apoptosis. In this study, microarray analyses was used to examine early changes in the downstream signal transduction pathways following the loss of lumicrine factors, and we discovered the following cascade of events leading to loss of protection and eventual apoptosis. First, mRNA expression of several key components of ERK pathway decreased sharply after 6 hours of loss protection from testicular lumicrine factors. After 12 hours, the levels of mRNA expression of STAT and NF-B pathways components increased, mRNA expression of genes encoding cell cycle inhibitors increased. After 18 hours of loss protection from testicular lumicrine factors, apoptosis was observed in the initial segment. In conclusion, testicular lumicrine factors protect the cells of the initial segment by activating ERK pathway, repressing STAT and NF-B pathways, and preventing a cascade of reactions leading to apoptosis.
Testicular lumicrine factors regulate ERK, STAT, and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Sex, Specimen part, Disease, Treatment
View SamplesGene-expression profiles of rat liver cirrhosis induced by diethylnitrosamine and the effect of erlotinib on liver fibrogenesis and liver cancer development
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Sex, Specimen part, Disease, Treatment
View SamplesGene-expression profiles of liver tissue of cabon tetrachloride (CCl4)-treated mouse and the effect of erlotinib
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Specimen part, Treatment
View SamplesGene-expression profiles of rat hepatocellular carcinoma induced by diethylnitrosamine (DEN) and the effect of erlotinib
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Specimen part, Treatment
View SamplesFCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, this protein is specifically expressed by memory B cells (MBCs) and is preferentially localized in subephitelial regions of lymphoid tissues. An expansion of FCRL4+ B cells has been shown in blood or other tissues in various infectious or autoimmune pathologies. In the present work, we generated and characterized in vitro FCRL4+ B cells from purified MBCs using T-dependent and/or T-independent stimulation. FCRL4+ B cells account for 17% of cells generated at day-4 of culture. Transcriptomic and phenotypic analysis of FCRL4+ cells show that they are closely related to FCRL4+ tonsillar MBCs. Interestingly, these cells highly express inhibitory receptors genes as described for exhausted FCRL4+ MBCs in the blood of HIV-viremic individuals. In agreement, in vitro generated FCRL4+ B cells show a significant underexpression of cell cycle genes with a two fold weaker number of cell division compared to FCRL4- cells. Finally, resulting from their reduced proliferation and differentiation potential, we show that FCRL4+ cells are not prone to generate plasma cells, contrary to FCRL4- cells. Given the difficulty to access to in vivo FCRL4+ cells, our in vitro model could be of major interest to study the biology of normal and pathological FCRL4+ cells.
Characterization of human FCRL4-positive B cells.
Specimen part
View SamplesMicroarray analysis was performed on retina/RPE/choroid samples taken from the right eyes of male chicks across control and recovery from form deprivation conditions.
Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/ choroid in chick model of form-deprivation myopia.
Sex, Specimen part, Treatment, Time
View SamplesBromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and NFkB target genes, which undermines the growth and survival of MCL cells. However, BETi treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4, which potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1, and the NFkB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the level of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared to ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Co-treatment of ARV-771 with ibrutinib or the BCL2-antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior pre-clinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or resistant MCL. Overall design: Twelve samples in biologic triplicates
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells.
Subject
View SamplesOne of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are established during development. In this paper, we use fluorescence activated cell sorting and RNA-seq to determine the transcriptome of the Drosophila CNS midline cells, which consist of a small number of well-characterized neurons and glia. These data revealed that midline cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and 31 small-molecule neurotransmitter receptor genes. In situ hybridization and high-resolution confocal analyses were carried-out to determine the midline cell identity for these neuropeptides and the neuropeptide receptors. The results revealed a surprising level of diversity. Neuropeptide genes are expressed in a variety of midline cell types, including motoneurons, GABAergic interneurons, and midline glia. These data revealed previously unknown functional differences among the highly-related iVUM neurons. There also exist segmental differences in expression for the same neuronal sub-type. Similar experiments on midline-expressed neuropeptide receptor genes reveal considerable diversity in synaptic inputs. Multiple receptor types were expressed in midline interneurons and motoneurons, and, in one case, link feeding behavior to gut peristalsis and locomotion. There were also segmental differences, variations between the 3 iVUMs, and three hormone receptor genes were broadly expressed in most midline cells. The Drosophila Castor transcription factor is present at high levels in iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor gene. Genetic and misexpression experiments indicated that castor specifically controls expression of the short neuropeptide F precursor gene, but does not affect iVUM cell fate or expression of Gad1. This indicates a novel function for castor in regulating neuropeptide gene expression. Overall design: To study the development and differentiation of the CNS midline cells of Drosophila melanogaster on a genome-wide scale, these cells were labeled with GFP using the GAL/UAS system and FACS purified at 2 ermbryonic time-points; 6-8 hours and 14-16 hours after egg laying. Poly(A) mRNA was collected from these samples and cDNA libraries were generated. Sequencing was performed on 6 independent samples: Two FACS purified CNS-midline cell samples and one non-midline sample taken from 6-8 hours After Egg Laying (AEL) embryos and from 14-16 hours AEL embryos.
Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation.
Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Research resource: progesterone receptor targetome underlying mammary gland branching morphogenesis.
Sex, Age, Specimen part, Treatment
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