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SRP125683
Homo sapiens
9 Downloadable Samples
Illumina HiSeq 2500
Description
Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Overall design: Serodiagnosis of pregnant women was done by means of conventional serological methods and carried out by the respective health centres based on routine assays. In maternal and umbilical cord blood samples T. cruzi presence was tested using multiplex Real Time PCR as previously described [6]. Maternal infection with other pathogens that produce congenital transmission and adverse pregnancy outcome were considered as exclusion criteria, as well as missing data or incorrect sampling. Fresh normal placentas were obtained after labour from vaginal or caesarean deliveries and placed within 24 hours at 4°C. Each placenta was dissected and the middle section [7] at 2 cm distance from the umbilical cord was isolated and placed into RNAlater solution (Applied Biosystems, Foster City, CA). Total RNA was extracted with TRIzol reagent (Invitrogen, Carlsbad, CA) and stored at -80°C until used. Transcriptomic studies. A RNA-Seq experiment was done in 9 pools of 2 different placental RNA samples each: 3 pools (C1, C2 and C3) belonging to placentas from seronegative mothers (SN) and 6 pools (TC4 to TC9) from seropositive mothers (SP). Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. The cDNA Libraries were prepared according to Illumina''s TruSeq Stranded Total RNA with Ribo-Zero Gold for Human and a Hiseq 2.500 Illumina platform with 100 bp paired-end reads was used for sequencing
Publication Title
Alterations in Placental Gene Expression of Pregnant Women with Chronic Chagas Disease.
Sample Metadata Fields
Subject
View Samples- Escherichia coli k-12
- 31 Downloadable Samples
Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
cAMP receptor protein (CRP, also known as the catabolite activator protein [CAP]) is arguably the best-studied of the global transcription factors of E coli. CRP alone is responsible for regulating at least 283 operons. Upon binding cAMP, the CRP dimer binds DNA and directly interacts with RNA polymerase (RNAP). At Class II promoters, CRP binds near position -41,5 relative to the transcription start site and contacts the amino-terminal domain of the RNAP subunit (RNAP-NTD). This interaction requires AR2, a patch of primarily positively charged residues (H19, H21, E96, and K101) that interact with negatively charged residues on RNAP-NTD. Acetylome analyses consistently detect lysine 100 (K100) of CRP as acetylated. Since K100 is adjacent to the positively charged AR2, we hypothesized that the K100 positive charge may also play a role in CRP function. We further hypothesized that acetylation of K100 would neutralize this positive charge, leading to a potential regulatory mechanism
Publication Title
Influence of Glucose Availability and CRP Acetylation on the Genome-Wide Transcriptional Response of <i>Escherichia coli</i>: Assessment by an Optimized Factorial Microarray Analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 52 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
We analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting.
Publication Title
Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
OBJECTIVE: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterize the role of tumor-initiating cells (T-ICs) and signaling pathways involved in sorafenib resistance. DESIGN: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: 1) Role of T-ICs by in vitro sphere formation and in vivo tumorigenesis assays using NOD/SCID mice, 2) Activation of alternative signaling pathways and 3) Efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, qRT-PCR) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in 2 independent cohorts. RESULTS: Sorafenib-acquired resistance tumors showed significant enrichment of T-ICs (164 cells needed to create a tumor) vs. sorafenib-sensitive tumors (13400 cells) and non-treated tumors (1292 cells), p<0.001. Tumors with sorafenib-acquired resistance were enriched with IGF and FGF signaling cascades (FDR<0.05). In vitro, cells derived from sorafenib-acquired resistant tumors and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumor growth and improved survival in sorafenib-resistant tumors. A sorafenib-resistance 175-gene signature was characterized by enrichment of progenitor-cell features, aggressive tumoral traits and predicted poor survival in 2 cohorts (n=442 HCC patients). CONCLUSION: Acquired resistance to sorafenib is driven by tumor initiating cells with enrichment of progenitor markers and activation of IGF and FGF signaling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression.
Publication Title
Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical interventions, which act mainly by regulating gene expression levels. A large fraction of patients (~30%), especially those of African descent, show a weak response to treatment. To interrogate the contribution of variable transcriptional response to inter-ethnic differences, we measured in vitro lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in peripheral blood mononuclear cells (PBMCs) from African-American and European-American healthy donors. We found that transcriptional response after 8hrs treatment was significantly correlated with variation in LGS within and between populations. We found that NFKB1, a gene previously found to predict LGS within populations, was more strongly downregulated in European-Americans on average. NFKB1 could not completely explain population differences, however, and we found an additional 177 genes with population differences in the average log2 fold change (FDR<0.05), most of which also showed a weaker transcriptional response in AfricanAmericans. These results suggest that inter-ethnic differences in GC sensitivity reflect variation in transcriptional response at many genes, including regulators with large effects (e.g. NFKB1) and numerous other genes with smaller effects.
Publication Title
Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Resveratrol, a natural phytoestrogen found in red wine and a variety of plants, is reported to have protective effects against lung cancer, however there is very little work directed towards the understanding of the mechanism of action of resveratrol in lung cancer. In this study we used an experimental approach to understand the biological activity and molecular mechanisms of resveratrol in A549 lung cancer cells. Gene expression profiles were compiled using an oligonucleotide microarray to determine altered expression levels in resveratrol treated cells.
Publication Title
Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Escherichia coli 8624 and the isogenic mutants in qseE, qseF and qseG are compared to determine the role that each of the genes play in regulation of the transcriptome. These results are verified by qRT-PCR and reveal the important role of this three-component signaling system.
Publication Title
The two-component system QseEF and the membrane protein QseG link adrenergic and stress sensing to bacterial pathogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Description
Pheochromocytomas/paragangliomas are the most heritable of all tumors. However, there are still cases that are not explained by mutations in the known genes. We aimed to identify the genetic cause of disease in a patient strongly suspected of having hereditary tumors. We identified a novel de novo mutation in DNMT3A, affecting a highly conserved residue. Among other results from other techniques, a different global expression profile was observed in the patient carrying the mutated DNMT3A compared to controls (parents) by RNA-seq
Publication Title
Gain-of-function mutations in DNMT3A in patients with paraganglioma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- NextSeq 500
Description
Upon fertilisation, the highly differentiated gametes reprogram to a totipotent state to initiate a new developmental programme. Approximately half of the mammalian genome is composed of repetitive elements, including retrotransposons, some of which are transcriptionally activated after fertilisation. It is generally assumed that retrotransposons become activated as a side-effect of the large chromatin remodelling underlying the epigenetic reprogramming of the gametes. Here, we have used a targeted epigenomic approach to address whether specific families of retrotransposons play a direct role in chromatin organisation and developmental progression after fertilisation. Using this approach, we demonstrate that precocious silencing of LINE-1 reduces chromatin accessibility, while their prolonged activation prevents gradual chromatin compaction, natural to developmental progression. Preventing LINE-1 activation and interfering with their silencing results in a reduced developmental rate independently of the coding nature of the LINE-1 transcript, suggesting that LINE-1 functions primarily at the chromatin level. Our data suggest that activation of LINE-1 regulates global chromatin accessibility at the beginning of development and indicate that activation of retrotransposons is an integral part of the developmental programme. Overall design: RNAseq was done on pooled injected embryos(4-5) as indicated in methods.
Publication Title
LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In a pilot experiment to reprogramme MEF into endoderm, we infected MEF with the Yamanakas factors (O: Oct4, K: Klf4, S: Sox2, M:Myc), FoxA2 (F) and Gata4 (G). Global gene expression of isolated clones was performed.
Publication Title
Gata4 blocks somatic cell reprogramming by directly repressing Nanog.
Sample Metadata Fields
No sample metadata fields
View Samples