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SRP198358
Homo sapiens
48 Downloadable Samples
Illumina HiSeq 2500
Description
We report a study about differentially expressed small non-coding RNAs in the blood of humans harboring a latent (LTBI) or active tuberculosis (TB) infection in comparison with exposed controls (ExC) and treated LTBI (LTBItt). All non-TB subjects enrolled in this study were recent close contacts (rCt) of a newly diagnosed contagious TB cases enrolled in Rio de Janeiro, Brazil. The detailed methodology is described below. According to Brazilian Ministry of Health (BMH) guidelines, the screen to detect LTBI among recent contacts comprises a clinical evaluation by a physician specializing in pulmonary diseases, a chest X-ray (CXR), and a tuberculin skin test (TST, cut-off 5mm). Additionally, as part of this study, blood was collected for short- (st) and long-term (lt) IGRA. St-IGRA was performed by stimulating whole blood with the Mtb antigen ESAT6:CFP10 (expressed as a fusion protein) for 22h (cut-off 10pg/mL). Lt-IGRA involved stimulating peripheral blood mononuclear cells (PBMC) with this same antigen for 5 days (cut-off 100 pg/mL). Cases were defined as follows: ExC were recent close contacts of a TB index case and had a negative response to both TST and in house interferon-gamma release assay (IGRA) by stimulating blood-derived specimens with ESAT6:CFP10 indicating absence of Mycobacterium tuberculosis (Mtb) infection. LTBI was defined as (1) a TST induration >5 mm measured 72 h after intradermal injection of Mtb purified protein derivative (PPD) and (2) a positive IGRA response (to either st-IGRA or lt-IGRA, or both) if indicators of active disease were observed on CXR, (3) the absence of acid-fast bacilli (AFB) and negative Lowenstein-Jensen (LJ) culture of clinical specimens were also required. LTBItt consisted of LTBI cases (TST+/IGRA+ at enrollment) who completed a 6-month course of IPT. Their blood samples were collected >2 months after the end of isoniazid (INH) preventive treatment (IPT). Active TB was defined as (1) respiratory symptoms suggestive of TB, and/or (2) detection of AFB and/or positive LJ culture in sputum, bronchoalveolar lavage or biopsy, followed by (3) remission of symptoms upon anti-TB chemotherapy. Their blood samples were obtained before initiation of treatment. Whole blood was collected in PAXgene RNA tubes (PreAnalytiX, SWZ) and was stored at -80°C for <2 years before RNA extraction. sncRNA libraries. Total RNA (including small RNA) was isolated using the PAXgene Blood miRNA Kit (PreAnalytiX, SWZ), which is indicated for the isolation and purification of total RNA longer than 18 nucleotides. The manufacturer’s instructions were followed at both stages. Total RNA was quantified with a Nanodrop ND-1000 spectrophotometer (Thermo Scientific, EUA) and RNA integrity was assessed via agarose gel electrophoresis. One microgram RNA was used for cDNA library preparation (TruSeq Small RNA Sample Preparation® Kit, Illumina, San Diego, CA) following the manufacturer’s protocols. RNAseq was performed on an Illumina HiSeq® 2500 Sequencing System (Illumina, San Diego, CA), generating 50 bp single reads and ≈16 million reads passing filter for each sample. Pre-processing and differential expression. The FASTQ files were preprocessed (FastQC 0.11.2), adaptors trimmed (Cutadapt 1.7.1), aligned to the human genome (STAR 2.4.1d), counted (featureCounts 1.4.6) on the Oasis 2.0 web platform. Transcripts with <5 reads in at least one sample were excluded. Then, normalized and evaluated for differentially expressed (DE) transcripts using DESeq2 (v. 1.16) on the Oasis 2.0 web platform (https://oasis.dzne.de/). Overall design: We collected blood samples from recent close contacts at recruitment and monitored them for 1 year. All TB cases were treatment-naïve. An active TB sncRNA signature was derived from whole blood RNA sequencing data by comparing TB and non-TB groups. Notably, it classified all TB cases correctly and reclassified 8 presumed LTBI cases as TB, 5 of whom turned out to have features of Mycobacterium tuberculosis infection on chest radiographs.
Publication Title
Reprogramming of Small Noncoding RNA Populations in Peripheral Blood Reveals Host Biomarkers for Latent and Active Mycobacterium tuberculosis Infection.
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Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
Description
We used microarrays to detail the global programme of gene expression dependent upon Stat3 in regulatory T cells
Publication Title
CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner.
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Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We are investigating the transcriptional response of mice infected with Helicobacter hepaticus and links to liver cancer
Publication Title
Genetic susceptibility to chronic hepatitis is inherited codominantly in Helicobacter hepaticus-infected AB6F1 and B6AF1 hybrid male mice, and progression to hepatocellular carcinoma is linked to hepatic expression of lipogenic genes and immune function-associated networks.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 91 Downloadable Samples
Description
Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of young adult mice treated with a single systemic dose of MAM display DNA damage (O6-methylguanine lesions) that peaks at 48 hours and decline to near-normal levels at 7 days post-treatment. By contrast, at this time, MAM-treated mice lacking the gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT), showed persistent O6-methylguanine DNA damage. The DNA damage was linked to cell-signaling pathways that are perturbed in cancer and neurodegenerative disease. These data are consistent with the established carcinogenic and developmental neurotoxic properties of MAM in rodents, and they support the proposal that cancer and neurodegeneration share common signal transduction pathways. They also strengthen the hypothesis that early life exposure to the MAM glucoside cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for medicine and/or food. Exposure to environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimers disease, as well as cancer.
Publication Title
The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.
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Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 51 Downloadable Samples
Description
The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin- Sca1+ c-kit+) stem cells while committed granulocyte-monocyte progenitors (GMPs) were transformation-resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll- AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 up-regulated expression of 196 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.
Publication Title
Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Neuroprotective therapies for retinal degeneration may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1 in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration.
Publication Title
Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 71 Downloadable Samples
Description
Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice.
Publication Title
Control of cognition and adaptive behavior by the GLP/G9a epigenetic suppressor complex.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Leukemias with MLL-rearrangements are characterized by high expression of the homeo box gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplant recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor.
Publication Title
A role for MEIS1 in MLL-fusion gene leukemia.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Wnt-4 signaling is critical for embryonic female sexual development. When Wnt-4 gene is deleted during embryonic development, the knock-out females present a partial sex reversal.
Publication Title
Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks
Publication Title
Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
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