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GSE20987
Mus musculus
12 Downloadable Samples
Description
To elucidate the mechanism of BCL6-mediated pre-B cell survival signaling, we investigated the gene expression pattern in BCR-ABL1-transformed BCL6+/+ and BCL6-/- B cell precursors. Pharmacological inhibition of BCR-ABL1 was performed with the BCR-ABL1 kinase inhibitor STI571 (Imatinib).
Publication Title
BCL6 is critical for the development of a diverse primary B cell repertoire.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Recurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid malignancies and in other cancers. However, the in vivo effects of Tet2 loss have not been delineated. We report here that Tet2 loss leads to increased stem-cell self-renewal and to progressive stem cell expansion. Consistent with human mutational data, Tet2 loss leads to myeloproliferation in vivo, notable for splenomegaly and monocytic proliferation. In addition, haploinsufficiency for Tet2 confers increased self-renewal and myeloproliferation, suggesting that the monoallelic TET2 mutations found in most TET2-mutant leukemia patients contribute to myeloid transformation. This work demonstrates that absent or reduced Tet2 function leads to enhanced stem cell function in vivo and to myeloid transformation.
Publication Title
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Activation of oncogenic ras pathway accounts for up to 90% low-grade superficial urothelial carcinomas of bladder, and p53 deficiency is very common in high-grade muscle invasive carcinomas. These two pathways in bladder urothelial tumorigenesis used to be considered divergent and their potential collaboration has not been illustrated.
Publication Title
Oncogenic HRAS Activates Epithelial-to-Mesenchymal Transition and Confers Stemness to p53-Deficient Urothelial Cells to Drive Muscle Invasion of Basal Subtype Carcinomas.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Tgif1 is a transcriptional corepressor that limits TGF responsive gene expression. TGF signaling has antiproliferative effects in several cell types, generally resulting in a G1 arrest. Mouse embryo fibroblasts (MEFs) are primary cells with limited life-span, that senesce after several passages in culture.
Publication Title
Premature senescence and increased TGFβ signaling in the absence of Tgif1.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
In this study, we have explored microarray-based differential gene expression profile in mouse lung tissue 8 h after inducing polymicrobial sepsis and the effect of preprotachykinin-A (PPTA) gene deletion. A range of genes differentially expressed (> 2-fold) in microarray analysis was assessed, PPTA-knockout septic mice with their respective sham controls.
Publication Title
Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
Description
DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum immunoglobulin levels. In vitro assays show that reduced immunoglobulin secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation but with an accelerated entry in cell division and an increase in class switch recombination. B cells from DREAM knockout mice did not show any phenotype, due to compensation by endogenous KChIP-2. Expression arrays revealed modified expression of Edem1 and Derlin3, two proteins related to the ER-associated degradation pathway and of Klf9, a cell-cycle regulator. Our results disclose a function of DREAM and KChIP-2 in Ig subclass production in B lymphocytes.
Publication Title
Increased B cell proliferation and reduced Ig production in DREAM transgenic mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
Description
As a critical cellular stress sensor, p53 mediates a variety of defensive processes including cell-cycle arrest, apoptosis, and senescence to prevent propagation of hyperproliferative cells or cells with a damaged genome, hence the formation of neoplasia. Transactivation of downstream genes plays an important while sometimes controversial role in regulating these cellular processes. To evaluate the dependence on transcriptional activation in p53s activities, we generated genetically-modified mouse lines carrying mutations in the transactivation domains (TADs) of p53. These transactivatio-deficient mutants serve as unique reagents to probe the dependence on robust transactivation in p53-mediated cellular functions, as well as the underneath mechanisms. To identify genes differentially regulated by these p53 mutants, we performed gene expression profiling analysis on mouse embryonic fibroblast cells (MEFs) from these mice in the context of oncogenic Ras-induced premature cellular senescence.
Publication Title
Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression.
Sample Metadata Fields
Specimen part
View Samples- 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.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 26 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Description
The Fragile X Mental Retardation Protein, FMRP, is thought to regulate the translation of a specific set of neuronal mRNAs on polyribosomes. Therefore, we prepared polyribosomes on sucrose gradients and purified mRNA specifically from these fractions, as well as the total mRNA levels, to determine whether a set of mRNAs might be changed in its % association with polyribosomes in the absence of FMRP in the KO mouse model.
Publication Title
FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism.
Sample Metadata Fields
Sex, Specimen part
View Samples