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GSE37901
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Data on the temporal dynamics of human placental gene expression is scarce. We have completed the first whole-genome profiling of human placental gene expression dynamics (GeneChips, Affymetrix) from early to mid- gestation (10 samples; gestational weeks 5 to 18) and report 154 genes with considerable change in transcript levels (FDR P<0.1). Functional enrichment analysis revealed >200 GO categories that are statistically over-represented among 105 genes with dynamically increasing transcript levels. Analysis in an extended sample (n=43; gestational weeks 5 to 41) conformed a highly significant (FDR P<0.05) expressional peak in mid-gestation placenta for ten genes: BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10, STC1. A central hypothesis of our study states that the aberrant expression of genes characteristic to mid-gestation placenta may contribute to affected fetal growth, maternal preeclampsia (PE) or gestational diabetes (GD). The gene STC1 coding for Stanniocalcin 1 (STC1) was identified with a sharp placental expressional peak in mid-gestation, increased mRNA levels at term and significantly elevated STC1 protein levels in post-partum maternal plasma in all pregnancy complications. The highest STC1 levels were identified in women, who developed simultaneously PE and delivered an SGA baby (median 731 vs 418 pg/ml in controls; P=0.001). CCNG2 and LYPD6 exhibited significantly increased placental mRNA expression and enhanced intensity of immunohistochemistry staining in placental sections all studied in GD and PE cases. Aberrant expression of mid-gestation specific genes in pregnancy complications at term indicates the importance of the fine-scale tuning of the temporal dynamics of transcription regulation in placenta. Observed significantly elevated plasma STC1 in complicated pregnancies warrants further investigations of its potential as a biomarker. Interestingly, a majority of genes with high expression in mid-gestation placenta have also been implicated in adult complex disease. This observation promotes a recently opened discussion on the role of placenta in developmental programming.
Publication Title
Mid-gestational gene expression profile in placenta and link to pregnancy complications.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
Illumina HiSeq 2500
Description
We report a pilot investigation for poly-A RNAs differentially expressed during Mycobacterium tuberculosis infection. Participation in this investigation from March 2010 to July 2013 was voluntary, only subjects that were >18 years old and that informed written consent were considered eligible. The recruitment of tuberculosis (TB) patients was done at public hospitals in Rio de Janeiro, Brazil. The diagnostic criteria for active pulmonary tuberculosis was at least one AFB (acid-fast bacilli) -positive sputum sample for M. tuberculosis and/or positive sputum culture and/or compatible clinical evolution for pulmonary TB and less than 15 days of anti-TB treatment and was in accordance with those of the Brazilian Ministry of Health. Blood was collected from recent close contacts (rCt) and active tuberculosis (TB) index cases (n=6). Latent TB infection (LTBI) was accessed by both tuberculin skin test (TST, cut-off = 5mm) and in house interferon-gamma release assays (IGRA, cut-off = 100 pg/ml), therefore, 12 rCt were classified as uninfected controls and 16 with LTBI. Subsequently, the sequencing was performed following the standard protocols on Illumina HiSeq® 2500 Sequencing System (Illumina, San Diego, CA) running 100 bp paired-end reads (PE100) and generating approximately 30 million reads passing filter for each sample to produce the mRNA reads. Mining these RNAseq data, highly prominent modulation of DOCK9, EPHA4, and NPC2 mRNA expression was observed in the TB samples, indicating that they might have a role in TB pathogenesis. These differential modulations upon M. Tuberculosis infection were further validated by additional evidences in larger cohorts from different geographical areas. Overall design: We collected blood samples from the recent close contacts (rCt) at the recruitment and monitored them for 1-year. All TB participants were treatment-naïve. An infection mRNA signature was derived from whole blood RNA sequencing data by comparing TB and uninfected rCt. We selected the 3 most prominent genes, by area under the ROC curve analysis, for additional validations. Some of the LTBI participants also showed the mRNA infection profile.
Publication Title
Transcriptomic Biomarkers for Tuberculosis: Evaluation of <i>DOCK9. EPHA4</i>, and <i>NPC2</i> mRNA Expression in Peripheral Blood.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 73 Downloadable Samples
- NextSeq 500
Description
Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive, and thus, novel techniques, including human microphysiological systems, or “organs on chips,” are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; yet clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development. Using a microphysiological system to model human kidney proximal tubule, we exposed cells to polymyxin B (PMB) and observed significant increases of injury signals, including kidney injury molecule-1 KIM-1and a panel of injury-associated miRNAs (each P < 0.001). Surprisingly, transcriptional profiling identified cholesterol biosynthesis as the primary cellular pathway induced by PMB (P = 1.2 ×10–16), and effluent cholesterol concentrations were significantly increased after exposure (P < 0.01). Additionally, we observed no upregulation of the nuclear factor (erythroid derived-2)–like 2 pathway despite this being a common pathway upregulated in response to proximal tubule toxicants. In contrast with PMB exposure, minimal changes in gene expression, injury biomarkers, and cholesterol concentrations were observed in response to NAB739 and NAB741. Our findings demonstrate the preclinical safety of NAB739 and NAB741 and reveal cholesterol biosynthesis as the novel (to our knowledge) pathway for PMB- induced injury. To our knowledge, this is the first demonstration of a human-on-chip platform used for simultaneous safety testing of new chemical entities and defining unique toxicological pathway responses of an FDA-approved molecule. Overall design: Cells from six donors were seeded into a total of 74 kidney chips, and effluents of kidney MPS were exposed for 48 hours of treatments
Publication Title
Human kidney on a chip assessment of polymyxin antibiotic nephrotoxicity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Androgens are a prequisite for the development of human prostate and prostate cancer. Androgen action is mediated via androgen receptor. Androgen ablation therapy is used for the treatment of metastasized prostate cancer. The aim of the study was to identify genes differentially expressed in benign human prostate, prostate cancer and in prostate tissue three days after castration. These genes are potential diagnostic and therapeutic targets for prostate cancer and benign prostatic hyperplasia.
Publication Title
Identification of androgen-regulated genes in human prostate.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina HiSeq 3000
Description
Understanding how differentiation, microenvironment, and hormonal milieu influence human breast cell susceptibility to malignant transformation will require the use of physiologically relevant in vitro systems. We developed a 3D culture model that enables the propagation of normal estrogen receptor alpha (ER)+ cells. The purpose of this experiment was to assess ER functionality and compare estrogen-induced transcripts among samples and systems. Overall design: RNA-seq was performed on RNA prepared from replicate 3D cultures from 3 normal 3D breast culture specimens exposed to 10nM estradiol or vehicle alone for 6 or 24 hours.
Publication Title
Propagation of functional estrogen receptor positive normal human breast cells in 3D cultures.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Rattus norvegicus
- 2 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Two major subsets of rat natural killer (NK) cells can be distinguished based on their expression of either the Ly49s3 or the NKR-P1B lectin-like receptor. Ly49s3+ NK cells, but not NKR-P1B+ NK cells, express a wide range of Ly49 receptors.
Publication Title
Two complementary rat NK cell subsets, Ly49s3+ and NKR-P1B+, differ in phenotypic characteristics and responsiveness to cytokines.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
DNA Damage Regulated Autophagy Modulator 1 (DRAM1) is a stress-inducible regulator of autophagy and cell death. DRAM1 has been implicated in cancer, myocardial infarction, and infectious diseases, but the molecular and cellular functions of this transmembrane protein remain poorly understood. Previously, we have proposed DRAM1 as a host resistance factor for tuberculosis (TB) and a potential target for host-directed anti-infective therapies. In this study, we generated a zebrafish dram1 mutant and investigated its loss-of-function effects during Mycobacterium marinum (Mm) infection, a widely used model in TB research. In agreement with previous knockdown analysis, dram1 mutation increased the susceptibility of zebrafish larvae to Mm infection. RNA sequencing revealed major effects of Dram1 deficiency on metabolic, immune response, and cell death pathways during Mm infection, whereas only minor effects on proteinase and metabolic pathways were found under uninfected conditions. Furthermore, unchallenged dram1 mutants did not display overt autophagic defects, while autophagic targeting of Mm was reduced in absence of Dram1, despite overall increased Lc3-II accumulation. The phagocytic ability of dram1 mutants was unaffected, but acidification of Mm-containing vesicles was strongly reduced, indicating that Dram1 is required for phagosome maturation. By in vivo imaging we observed that Dram1-deficient macrophages fail to restrict Mm during early stages of infection. The resulting enhanced bacterial burden phenotype could be rescued by knockdown of inflammatory caspase (caspa) and gasdermin (gsdmeb), demonstrating pyroptosis as the mechanism underlying premature cell death of Mm-infected macrophages in dram1 mutants. Collectively, these data demonstrate that dissemination of mycobacterial infection in zebrafish larvae is promoted in absence of Dram1 due to reduced maturation of mycobacteria-containing vesicles, failed intracellular containment, and consequent pyroptotic cell death of infected macrophages. These results provide new evidence that Dram1 plays a central role in host resistance to intracellular infection, acting at the crossroad of autophagy and cell death. Overall design: Mutant embryos and their controls were manually dechorionated at 24 hours post fertilization (hpf) and at 28 hpf they were infected by injecting 150 or 300 colony forming units of M. marinum strain M into the blood island, or mock-injected with PBS/2%PVP. After injections embryos were transferred into fresh egg water containing 0.003% 1-phenyl-2-thiourea (Sigma-Aldrich) to prevent melanisation and incubated for 4 days at 28,5°C. After the incubation period, infected and uninfected mutants and their controls were imaged and groups of 20 embryos were snap-frozen in liquid nitrogen and RNA was isolated for Illumina RNAseq analysis.
Publication Title
Deficiency in the autophagy modulator Dram1 exacerbates pyroptotic cell death of Mycobacteria-infected macrophages.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The noncluster homeodomain containing gene, HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell Acute Lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgH-TLX1Tg mice, which developed mature B cell lymphoma after a long latency period suggesting the requirement of additional mutations to initiate malignancy.
Publication Title
Ectopic TLX1 expression accelerates malignancies in mice deficient in DNA-PK.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Sequencing of 5'' ends of RNA molecules from control and exosome-depleted S2 cells. Overall design: CAGE library construction from RNA extracted from control and exosome-depleted cells.
Publication Title
Transcription start site analysis reveals widespread divergent transcription in D. melanogaster and core promoter-encoded enhancer activities.
Sample Metadata Fields
Subject
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq4000
Description
RNA sequencing was performed on RNA isolated from groups of 6 hpf wild type and mecp2-null embryos (n=3 biological replicates per condition with 30 embryos pooled per replicate). DESeq2 analysis was performed using https://usegalaxy.org/ Overall design: Whole embryo mRNA profile of 30 pooled mecp2-null or wild type 6 hpf zebrafish embryos, in triplicate, using the Illumina HiSeq4000 platform
Publication Title
Mecp2 regulates <i>tnfa</i> during zebrafish embryonic development and acute inflammation.
Sample Metadata Fields
No sample metadata fields
View Samples