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SRP071580
Mus musculus
14 Downloadable Samples
NextSeq 500
Description
Acute myeloid leukemia (AML) is associated with poor prognosis, and there is a strong need to develop new therapeutic strategies to improve treatments. We performed a cytokine screen with 114 recombinant proteins to identify selective negative regulators of primitive murine AML cells relative to normal bone marrow cells. The top candidate identified was interleukin 4 (IL4), as it showed the most selective inhibition of leukemia cell growth. Stimulating leukemia cells ex vivo with IL4 and transplanting the cells into mice resulted in reduced leukemia burden and prolonged survival compared with controls. In contrast, IL4 did not inhibit the function of normal hematopoietic stem and progenitor cells in long-term bone marrow repopulation assays. Moreover, we found that IL4 treatment of leukemia cells induced Stat6 phosphorylation, and that leukemia cells with Stat6 knocked out using CRISPR/Cas9-genetic engineering were partially resistant to IL4 stimulation, revealing Stat6 as a critical mediator of the IL4 effect. To evaluate whether IL4 has in vivo therapeutic efficacy, we expressed IL4 ectopically in leukemia cells in vivo and also injected IL4 into leukemic mice; both strategies resulted in the suppression of the leukemia cell burden and increased survival. Further analysis revealed that IL4 treatment induces apoptosis in the leukemia cells. Importantly, IL4 exposure also inhibited the growth and survival of primary AML patient cells. In summary, these findings demonstrate that IL4 selectively inhibits AML cells in a Stat6-dependent manner, thus revealing IL4 as a candidate therapeutic agent in AML. IL4 (ProSpec, East Brunswick NJ, USA) was resuspended following the provider guidelines and stored in aliquotes at -80 °C. Mouse MLL-AF9 leukemia cells were provided by Dr. Benjamin Ebert (Brigham and Women’s Hospital, Boston MA, USA). The murine leukemia cells were cultured in SFEM (StemCell Tech) supplemented with 1% penicillin/streptomycin at 37 °C with 5% CO2. Overall design: Mouse MLL-AF9 leukemia cells were grown in 20 ng/mL IL3 with or without IL4 (100 ng/mL) for 18 hours.
Publication Title
Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 303 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study gene expression profiles for 307 cases of advanced bladder cancers were compared to molecular phenotype at the tumor cell level. TUR-B tissue for RNA extraction was macrodissected from the close vicinity of the tissue sampled for immunohistochemistry to ensure high-quality sampling and to minimize the effects of intra-tumor heterogeneity. Despite excellent agreement between gene expression values and IHC-score at the single marker level, broad differences emerge when samples are clustered at the global mRNA versus tumor cell (IHC) levels. Classification at the different levels give different results in a systematic fashion, which implicates that analysis at both levels is required for optimal subtype-classification of bladder cancer.
Publication Title
Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
TK2 deficiency causes severe mtDNA depeltion in several tissues, including skeletal muscle and heart. TK2 knockout mice grow slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal size.
Publication Title
Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer.
Publication Title
Molecular subtype classification of urothelial carcinoma in Lynch syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We isolated and selected intestinal adenoma organoids from Apcmin/+; Rosa26LSL-TdTomato; Prox1-CreERT2 mice. After the selection procedure without growth factors, we induced CreERT2 activity and the transcription of tdTomato to label Prox1+ cells by 300 nM 4-hydroxytamoxifen for 16h. tdTomato+ (Prox1+) and tdTomato- cells (enriched for Prox1- cells) were FACS sorted and total RNA was isolated.
Publication Title
Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-like Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
41 volunteers (male non-smokers) were exposed to formaldehyde (FA) vapors for 4 h per day over a period of 5 working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 ppm. At concentrations of 0.3 ppm and 0.4 ppm, four peaks of 0.6 or 0.8 ppm for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (about 80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange (SCE) test and the cytokinesis-block micronucleus test (CBMNT) were performed with blood samples. The micronucleus test (MNT) was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time RT-PCR with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. None of the tests performed showed a biologically significant effect related to FA exposure. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA also did not cause biologically relevant alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.
Publication Title
Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We isolated and selected intestinal adenoma organoids from villin-CreER; Apcflox/flox and villin-CreER; Apcflox/flox; Prox1flox/flox mice and added tamoxifen to induce the deletion of the Apc and Prox1 genes in the intestinal epitheliul ex vivo. Microarray experiments were carried out 7 days after the addition of tamoxifen.
Publication Title
Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-β.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Intestinal crypts isolated from Apcflox/flox; villin-CreERT mice were treated with Tamoxifen to induce the deletion of Apc. Tamoxifen-treated organoids were selected in the absence of Wnt agonists and then treated with TGF-beta.
Publication Title
Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-β.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Danio rerio
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
We sequenced strand-specific mRNA from the heads of 3 groups of wild type zebrafish (Danio rerio) 5 days post fertilization. Overall design: Examination of the relative expression of genes in the developing zebrafish brain
Publication Title
BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies.
Sample Metadata Fields
No sample metadata fields
View Samples