Mutations in the gene encoding surfactant protein C (SFTPC) have been linked to interstitial lung disease in children and adults. Expression of the index mutation, SP-Cdeltaexon4, in transiently transfected cells and type II cells of transgenic mice resulted in misfolding of the proprotein, activation of ER stress pathways and cytotoxicity. In the current study we show that stably transfected cells adapted to chronic ER stress imposed by constitutive expression of SP-Cdeltaexon4 via an NF-kB-dependent pathway. However, infection of cells expressing SP-Cdeltaexon4 with respiratory syncytial virus resulted in significantly enhanced cytotoxicity associated with accumulation of the mutant proprotein, pronounced activation of the unfolded protein response and cell death. Adaptation to chronic ER stress imposed by misfolded SP-C was associated with increased susceptibility to viral-induced cell death. The wide variability in the age of onset of ILD in patients with SFTPC mutations may be related to exposure to an environmental insult that ultimately overwhelms the homeostatic, cytoprotective response.
Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C.
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View SamplesEstrogen receptor- (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of this transcription factor using the Affymetrix Genechip Mouse Genome 430-2.0 arrays.
Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome.
Sex, Specimen part, Treatment
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Comparison of four ChIP-Seq analytical algorithms using rice endosperm H3K27 trimethylation profiling data.
Specimen part
View SamplesImmatured rice seeds 7-8 days after pollination were used for expression analysis and matured rice leaf was used as control.
Comparison of four ChIP-Seq analytical algorithms using rice endosperm H3K27 trimethylation profiling data.
Specimen part
View SamplesReproductive success depends on a functional oviduct for gamete storage, maturation, fertilization, and early embryonic development. The ovarian-derived sex steroids estrogen and progesterone have been found to influence cell proliferation, differentiation and functionality of the oviduct. The objective of this study was to investigate steroidal regulation of oviductal epithelial cell function by using the Bovine Gene 1.0 ST array (Affymetrix Inc., CA) for transcriptional profiling. Our overall goals were to increase our understanding of known epithelial cell processes critical for fertility, and to identify novel genes and biochemical processes for future analysis. Transcripts were annotated using NetAffx annotation database for the Bovine gene 1.0 ST array and last updated in June 2014.
A transcriptomal analysis of bovine oviductal epithelial cells collected during the follicular phase versus the luteal phase of the estrous cycle.
Specimen part
View SamplesOBJECTIVE: Acromegaly is a rare endocrine disorder with excess growth hormone (GH) production. This disorder has important metabolic effects in insulin resistance and lipolysis. The objective of this study was to explore transcriptional changes induced by GH in adipose tissue. METHODS: The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex-vivo for lipolysis and ceramide levels. Adipose tissue was analyzed by RNA sequencing (RNA-seq). RESULTS: There was evidence of reduced insulin sensitivity based on the increase in fasting glucose, insulin and HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3) as well as several novel transcriptional changes, some of which may be important for GH signal regulation (PTPN3 and PTPN4) and the effect of GH on growth and proliferation. Several transcripts could potentially be important in GH-induced metabolic changes. Specifically, induction of LPL, ABHD5, and ACVR1C could contribute to enhanced lipolysis and may explain the suggestive enhancement of adipose tissue lipolysis in acromegaly patients as reflected by glycerol release from the explants of the two groups of patients (p=0.09). Higher expression of SCD and TCF7L2 could contribute to insulin resistance. Expression of HSD11B1 was reduced and GR was increased, predicting modified glucocorticoid activity in acromegaly. CONCLUSIONS: We identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. Overall design: DESIGN: Patients with acromegaly (n=9) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012. Sequencing was performed on RNA from 7 acromegaly patients and 11 controls.
Gene Expression Signature in Adipose Tissue of Acromegaly Patients.
No sample metadata fields
View SamplesIn many parts of the US, selenium (Se)-deficient soils dictate the necessity of supplementing this trace mineral directly to the diet of cattle, with the form of Se supplied known to affect tissue-level gene expression profiles and presumably function. Because a deficiency of Se will reduce fertility, including reduced biosynthesis of testosterone by the testis and an increased frequency of abnormalities in mature spermatozoa, we hypothesized that the form of Se supplemented to cows during gestation would affect the transcriptome of the neonatal bull calf testis. Microarray analysis using the Bovine gene 1.0 ST array (GeneChip; Affymetrix, Inc., Santa Clara, CA) was conducted to determine whether gestational form of supplemental Se affected gene expression profiles in the testis. GeneChip transcript annotations were last updated in January 2013 using the annotation update release 33 from the NetAffx annotation database.
Gestational form of Selenium in Free-Choice Mineral Mixes Affects Transcriptome Profiles of the Neonatal Calf Testis, Including those of Steroidogenic and Spermatogenic Pathways.
Specimen part
View SamplesCell migration contributes to normal development and homeostasis as well as to pathological processes such as inflammation and tumor metastasis. Previous genetic screens have revealed a few major signaling pathways that govern follicle cell migrations in the Drosophila ovary, several of which elicit transcriptional responses. However few downstream targets of the critical transcriptional regulators, such as the C/EBP homolog SLBO, have been identified. To characterize the gene expression profile of two migratory cell populations and identify SLBO targets, we employed a magnetic bead based cell separation approach to purify border cells and centripetal cells expressing the mouse CD8 antigen, and carried out whole genome microarray analysis.
Analysis of cell migration using whole-genome expression profiling of migratory cells in the Drosophila ovary.
Sex, Specimen part
View SamplesIn this study, we studied the genomic responses of the Insig and Scap deletion from perinatal lung.
Epithelial SCAP/INSIG/SREBP signaling regulates multiple biological processes during perinatal lung maturation.
Specimen part
View SamplesUsing RNA-Seq, we compared the transcriptomes of muscle from wild type C57BL/6J or Zp407 transgenic mice. Overall design: Biceps femoris were stored in RNAlater from 5-week-old overnight-fasted male mice. 5 mice were used per group for wild type and Zp407 transgenic mice.
Zinc finger protein 407 overexpression upregulates PPAR target gene expression and improves glucose homeostasis in mice.
Sex, Age, Specimen part, Subject
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