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SRP067973
Caenorhabditis elegans
20 Downloadable Samples
Illumina HiSeq 2500
Description
Purpose: The goal of this study is to understand how dbl-1, which is made primarily in neurons, and hrg-7, which is exclusively made in the intestine, contribute to systemic heme homeostasis. Methods: mRNA profiles of late L4 dbl-1(nk3) and hrg-7(tm6801) mutant C. elegans fed OP50 E. coli or OP50 + 50µM heme were compared to mRNA profiles from wildtype (WT) broodmates. Profiles were generated with single-end 50 base reads obtained using Illumina’s HiSeq 2500. Bioinformatics quality control was performed followed by alignment of reads to the ce10 reference genome using Tophat2, version 2.1.0. We found differentially expressed genes using Cufflinks 2, version 2.2.1 with a cutoff of 0.05 on False Discovery Rate (FDR). Results: We found a substantial overlap of genes regulated by both dbl-1 and hrg-7, including 49 heme-responsive genes (hrgs) in low heme (OP50) and 11 hrgs in high heme (OP50 + 50µM). Additionally, our data indicate crosstalk between dbl-1 and hrg-7 signaling. dbl-1 directly regulates hrg-7 expression, while hrg-7 regulates three components of the dbl-1 signaling pathway. Conclusions: Our study demonstrates that communication between the neuron and intestine is essential for heme homeostasis. Specifically, we report that HRG-7 functions as a secreted signaling factor which communicates intestinal heme status with extraintestinal tissues by integrating a DBL-1/BMP -dependent response from the neurons to transcriptionally regulate genes involved in heme homeostasis. Cellular requirements for heme are fulfilled by a cell’s internal capacity to synthesize its own heme in a cell-autonomous manner. However, growing evidence in vertebrates predicts that cellular heme levels in animals are not only maintained by heme synthesis, but also by distally located proteins that could signal systemic heme requirements to an inter-organ heme trafficking network through cell-nonautonomous regulation. Using C. elegans, a genetically and optically amenable animal model for visualizing heme-dependent signaling, we show that HRG-7, an aspartic protease homolog, mediates inter-organ signaling between the intestine and neuron. Loss of hrg-7 results in robust expression of intestinal heme importers and, remarkably, this occurs even under heme replete conditions when such transporters are not normally expressed. HRG-7 functions as a secreted signaling factor, independent of a functional enzymatic active site, and communicates intestinal heme status with extraintestinal tissues by integrating a DBL-1/BMP -dependent response from the neurons to transcriptionally regulate intestinal heme homeostasis. Given the evidence indicating that mechanisms of heme transport are conserved across metazoa, it is conceivable that the cell-nonautonomous signaling framework that we uncovered in C. elegans may have functional relevance for inter-organ regulation of iron and heme metabolism in humans. Overall design: Comparison of mRNA profiles from dbl-1(nk3) mutant C. elegans vs. wildtype (WT) broodmates and hrg-7(tm6801) mutants vs (WT) broomates fed OP50 E. coli or OP50 + 50µM heme. Biological duplicates were analyzed for dbl-1(nk3) mutants and (WT) broodmates. Biological triplicates were analyzed for hrg-7(tm6801) mutants and (WT) broodmates.
Publication Title
Inter-organ signalling by HRG-7 promotes systemic haem homeostasis.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection.
Publication Title
Down-regulation of intra-hepatic T-cell signaling associated with GB virus C in a HCV/HIV co-infected group with reduced liver disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Signalling via the colony stimulating factor 1 receptor (CSF1R) controls the survival, differentiation and proliferation of macrophages which are a source of the somatic growth factor insulin growth factor 1 (IGF1). Treatment of newborn mice with CSF1 has previously been shown to produce an increase in somatic growth rate and we hypothesised that treatment of neonatal low birth weight (LBW) rats with CSF1 would do the same. Growth rates were not affected, yet CSF1 treatment caused an unexpectedly large, but reversible increase in liver size and hepatic fat deposition in both normal and LBW rats. By transcriptional profiling, we have highlighted numerous CSF1-regulated genes known to be involved in lipid droplet formation in the liver and novel candidate genes for further investigation. In contrast to mice and weaner pigs, CSF1 treatment did not increase hepatocyte proliferation in neonatal rats, rather the data were consistent with increased macrophage proliferation instead. This suggests that Kupffer cells promote lipid accumulation in neonates and treatment to ablate CSF1R signalling may reverse lipid accumulation in the liver.
Publication Title
Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients by viral vector-mediated factor transduction represent a powerful tool for biomedical research and may provide a source for cell replacement therapies. However, the proviruses encoding the reprogramming factors represent a major limitation of the current technology because even low vector expression may alter the differentiation potential of the iPSCs and induce malignant transformation. Here we show that fibroblasts from five patients with idiopathic Parkinsons disease (PD) can be efficiently reprogrammed into hiPSCs and subsequently differentiated into dopaminergic neurons. Moreover, we derived PD specific hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Upon factor deletion these cells maintain a pluripotent state and intact karyotype. Importantly, these factor-free hiPSCs show a global gene expression profile, which is more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in conventional virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease.
Publication Title
Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 24 Downloadable Samples
- IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Purpose: To identify differntially expressed transcripts in TP-0903 treated embryos that impair cranila NC EMT and cell migration in zebrafish embryos Methods: zebrafish embryos treated at 13 hpf with 5-7uM TP-0903 and DMSO for 1-, 4- and 8-hrs at 28°C. 35 embryos were collected for each treatment. Results: TP-0903 increases expression of several retinoic acid target genes including genes from within the retinoid pathway Conclusions: TP-0903 causes a direct increase in RA signaling that impairs cranial NC EMT and cell migration in zebrafihs embryos Overall design: mRNA profiles of zebrafish embryos treated with TP-0903 and DMSO were generated by RNA-Seq, in quadruplicates, using Illumina Hi Seq
Publication Title
Phenotypic chemical screening using a zebrafish neural crest EMT reporter identifies retinoic acid as an inhibitor of epithelial morphogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 14 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
A first generation Affymetrix GeneChip Porcine genome array was used to profile the gene expression in porcine mesenteric lymph nodes over a time course of infection with S. Typhimurium, including the acute (8 hours post inoculation (hpi), 24 hpi, 48 hpi) and chronic (21 days post-inoculation (dpi)) stages of infection. Our objectives were to 1) identify and examine the stereotypical gene expression response within host MLN to S. Typhimurium infection, 2) characterize global host responses by revealing the specific features of the hosts innate immunity pathways, and 3) explore if and how S. Typhimurium may escape the host immune response and develop into a carrier state.
Publication Title
Global transcriptional response of porcine mesenteric lymph nodes to Salmonella enterica serovar Typhimurium.
Sample Metadata Fields
Age
View Samples- Sus scrofa
- 14 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
To understand the host transcriptional response to S. enterica serovar Choleraesuis (S. Choleraesuis), the first generation Affymetrix porcine GeneChip was used to identify differentially expressed genes in the mesenteric lymph nodes responding to infection at acute (8 hours (h), 24h, 48h post-inoculation (pi)) and chronic stages (21 days (d) pi)
Publication Title
Analysis of porcine transcriptional response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the mesenteric lymph node.
Sample Metadata Fields
Age
View Samples- Sus scrofa
- 19 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of this gram-negative bacteria in such pigs is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we have initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n=40) was inoculated with ST and the peripheral blood and feces were collected between 2 and 20 days post-inoculation. Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. The global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip?analysis of peripheral blood RNA at day 0 and day 2 post-inoculation.
Publication Title
Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: intersection of IFNG, TLR and miRNA pathways.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Organelles such as endoplasmic reticulum (ER) and mitochondria interact with each other at specialized domains on the ER known as mitochondria-associated membranes (MAMs). Here, using three-dimensional high-resolution imaging techniques, we show that the Sel1LHrd1 protein complex, the most conserved branch of ER-associated protein degradation (ERAD), exerts a profound impact on ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover and hence the abundance of the MAM protein sigma receptor 1 (SigmaR1). Sel1L or Hrd1 deficiency in brown adipocytes impairs dynamic interaction between ER and mitochondria, leading to the formation of pleomorphic “megamitochondria” and, in some cases with penetrating ER tubule(s), in response to acute cold challenge. Mice with ERAD deficiency are cold sensitive and exhibit mitochondrial dysfunction in brown adipocytes. Mechanistically, endogenous SigmaR1 is targeted for proteasomal degradation by Sel1L-Hrd1 ERAD, whose accumulation in ERAD-deficient cells leads to mitofusin 2 (Mfn2) oligomerization, thereby linking ERAD to mitochondrial dynamics. Our study identifies Sel1L-Hrd1 ERAD as a critical determinant of ER-mitochondria contacts, thereby regulating mitochondrial dynamics and thermogenesis.
Publication Title
Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We identified tazarotene-induced gene 1 (TIG1) as a potential tumorigenic gene in IBC. To investigate the underlying mechanism by which TIG1 promotes tumor growth and invasiveness of IBC cells, we first sought to identify TIG1 functional partners by using DNA microarray analysis to compare gene expression profiles between SUM149 cells transfected with control siRNA and SUM149 cells transfected with siRNA targeting TIG1. We identified receptor tyrosine kinase Axl as a functional partner of TIG1.
Publication Title
TIG1 promotes the development and progression of inflammatory breast cancer through activation of Axl kinase.
Sample Metadata Fields
Cell line
View Samples