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GSE39955
Mus musculus
42 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To model the effect of Pten loss on breast cancer, we deleted Pten using a floxed allele and the deleter lines MMTV-Cre(NLST), which targets stem/bi-potent progenitor cells, and WAP-Cre, which targets CD24-positive, pregnancy-identified stem cells/alveolar progenitors. Mammary tumors were detected in WAP-Cre:Ptenf/f females with a latency of 15.2 months. By 18 months, nearly all mice had succumbed to cancer. MMTV-Cre:Ptenf/f mice developed mammary tumors after a longer latency of 26.4 months and reduced penetrance (70%) compared to WAP-Cre:Ptenf/f mice. Tumors from both models were heterogeneous, consisting primarily of differentiated adenocarcinoma (adenomyoepithelioma; ~70%) and adenosquamous carcinoma (20-25%). In addition, a small fraction of tumors was classified as acinar and poorly differentiated adenocarcinoma (4-7%) and adenosarcoma (3-4%). To test the consequences of combined Pten and p53 gene mutation on breast cancer, we deleted both genes via MMTV-Cre or WAP-Cre. Kaplan-Meier tumor free survival curves revealed that WAP-Cre:Ptenf/f:p53f/f and MMTV-Cre:Ptenf/f:p53f/f females developed tumors with reduced latency of 11.3 and 9.8 months, compared with 15.2, 26.4, and 16.9 months for single-mutant WAP-Cre:Ptenf/f, MMTV-Cre:Ptenf/f or MMTV-Cre:p53f/f mice, respectively. In contrast to the heterogeneity of Pten tumors and small percentage of adenosarcomas in these mice, ~70% of Pten:p53 lesions were histologically classified as adeno-sacrcomatoid-like or mesenchymal-like breast cancer, with the rest exhibiting mixed mesenchymal plus adenocarcinomas and differentiated adenocarcinomas. The adeno-sacrcomatoid-like tumors expressed the mesenchymal markers vimentin, K5, SMA, N-cadherin and desmin but not ER, as well as islands of luminal-like K18 expressing cells surrounded by a layer of K14-positive cells.
Publication Title
Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Microarray analysis was performed at the UHN Microarray Centre (UHNMAC, Ontario, Canada) using Illumina HumanHT-12 v4 BeadChip with 500 ng of total RNA prepared by RNeasy mini kit (QIAGEN, Cat. No. 74104). Samples from HCC1954 cells with 3-day treatment of TBK1-II at 4 uM were used to compare with vehicle-treated controls. Microarray data was processed and normalized by lumi package from BioConductor in R with Quantile Method. Difference between the samples were calculated by Bayesian statistic using limma package from BioConductor in R to obtain Moderated T value for subsequent Pathway analysis.
Publication Title
shRNA kinome screen identifies TBK1 as a therapeutic target for HER2+ breast cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
Ion Torrent S5
Description
We investigated whether in vitro expansion of human alveolar epithelial type II cells is possible. We found that human endogenous human alveolar epithelial type II cells can be cultured and passaged. The culture system enabled retroviral gene transduction into human alveolar epithelial type II cells. We performed RNA sequencing of human alveolar epithelial type II cells transduced with mutant surfactant protein C or control vector. Overall design: Cultured human alveolar epithelial type II cells were transfected with retroviral vector containing mutant surfactant protein C or control retroviral vector. The retroviral vector contained LNGFR as a marker. After gene transduction, transduced cells were purified by magnetic-activated cell sorting. The transcriptome of the cells was generated by 5'Tag-seq using Ion Genestudio S5 Sequencer.
Publication Title
In vitro expansion of endogenous human alveolar epithelial type II cells in fibroblast-free spheroid culture.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Ion Torrent Proton
Description
In the alveoli, lung fibroblasts are in close contact with alveolar epithelial cells type 2, and are considered to support alveolar epithelial cells, forming an alveolar stem cell niche. However, what fibroblast-to-epithelial cell interactions occur during the alveolar maturation stage remains unclear. To understand the lung fibroblast-to-epithelial cell interactions, we performed time-course 3´SAGE-seq analysis of lung epithelial cells and fibroblasts. Overall design: Lung epithelial cells and lung fibroblasts from various developmental stages (E18.5, P0.5, P2, P7, P28, and P56) were purified by cell sorting. The time series transcriptome of the epithelial cells and fibroblasts was generated by 3'SAGE-seq using Ion Proton sequencer.
Publication Title
Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
We reported this study established a mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. Overall design: kidney mRNA profiles of Olive oil, CCl4, EtOH, and CCl4+EtOH treatment in C57BL/6 mice were generated by deep sequencing.
Publication Title
A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Iron is an essential nutritional element; its deficiency in the body causes nutritional problems and a decrease in iron storage that can lead to anemia. The liver not only stores iron but is an important metabolic target as well. Dietary iron deficiency is associated with changes in the metabolism of nutrients such as lipids. However, to the best of our knowledge, a global analysis detailing the consequences of iron deficiency in the body has not yet been reported. We performed a comprehensive transcriptome analysis using DNA microarray technology to reveal the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet or a control diet for 16 days. On day 17, the rats were sacrificed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 up-regulated and 500 down-regulated probe sets to characterize the iron-deficient diet group. The up-regulated probe sets contained genes for enzymes that are involved in cholesterol, amino acid, and glucose metabolisms, as well as in apoptosis. The down-regulated probe sets included genes for enzymes associated with lipid metabolism. Additionally, the 16-day iron-deficient diet induced anemia. Our gene expression analysis revealed that, as a result, cholesterol biosynthesis, gluconeogenesis, and apoptosis due to endoplasmic reticulum stress were accelerated, while fatty acid biosynthesis was suppressed by dietary iron deficiency. Our analysis also showed that cholesterol metabolism, including bile acid biosynthesis, was accelerated in the initial stages of cholesterol accumulation.
Publication Title
Dietary iron-deficient anemia induces a variety of metabolic changes and even apoptosis in rat liver: a DNA microarray study.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Intratracheal transfer of isolated lung fibroblasts in bleomycin-induced lung fibrosis recapitulates the activation process of lung fibroblasts after epithelial injury. In order to investigate gene expression signatures of transferred fibroblasts, we purified transferred fibroblasts 2, 4, and 7 days after the transfer and performed transcriptome analysis. We also isolated Acta2 high and low cells by using Acta2-mKO1 reporter mice 4 days after the transfer. Overall design: Lung fibroblasts were isolated from untreated Col-GFP mice after tissue dissociation and negative selection for lineage markers. Isolated lung fibroblasts were intratracheally transferred into wild type mice, which received intratracheal bleomycin treatment 7 days before the transfer. Col-GFP+ cells were purified from the host lungs by FACS sorting on 2, 4, and 7 days after the transfer. Acta2 high and low cells were prepared by transferring lung fibroblasts from Acta2-mKO1 reporter mice. mRNA was isolated from sorted cells, and gene expression profiles were acquired by next generation sequencing.
Publication Title
Gli signaling pathway modulates fibroblast activation and facilitates scar formation in pulmonary fibrosis.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Lung fibroblasts play a pivotal role in pulmonary fibrosis, a devastating lung diseases, by producing extracellular matrix. MicroRNAs (miRNAs) suppress a lot of genes posttranscriptionally, but the dynamics and the role of miRNAs in activated lung fibroblasts in fibrotic lung has been poorly understood. We found miR-19a, 19b and 20a subcluster expression increased in activated lung fibroblasts as the fibrosis progression. To elucidate whether fibroblast-specific intervention against miR-19a, 19b and 20a subcluster modulates pathogenic activation of lung fibroblasts in vivo, we intratracheally-transferred the subcluster-overexpressed fibroblasts into bleomycin-treated lungs and performed global transcriptome analysis. Overall design: miR-19a, 19b and 20a subcluster-overexpressed fibroblasts and mock-expressed fibroblasts were intratracheally-transferred to B6 mice at day 7 post-administration of 2 mg/kg of bleomycin. Donor cells were recoverred at day 3 post-transfer by cell sotring. Global transcriptome of transferred fibroblasts was generated by 3'SAGE-seq using Ion Proton sequencer.
Publication Title
Lung fibroblasts express a miR-19a-19b-20a sub-cluster to suppress TGF-β-associated fibroblast activation in murine pulmonary fibrosis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Expression profiles in mouse liver exposed to long-term gamma-irradiation were examined to assess in vivo effects of low dose-rate radiation. Three groups of male C57BL/6J mice were exposed to whole body irradiation at dose-rates of 17-20 mGy/day, 0.86-1.0 mGy/day or 0.042-0.050 mGy/day for 401-485 days (cumulative doses were approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively).
Publication Title
Gene expression profiles in mouse liver after long-term low-dose-rate irradiation with gamma rays.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although lung fibroblasts play central roles in PF, their key regulatory molecules remain unclear. We performed transcriptome analysis of lung fibroblasts from bleomycin- and silica-treated murine lungs and identified 55 hub transcription factors highly connected to gene modules differentially expressed in PF. To elucidate whether fibroblast-specific intervention against the hub transcription factor Srebf1 modulates pathogenic activation of lung fibroblasts in vivo, we intratracheally-transferred active form of Srebf1-overexpressed fibroblasts into bleomycin-treated lungs and performed global transcriptome analysis. Overall design: Active form of Srebf1-overexpressed fibroblasts and mock-expressed fibroblasts were intratracheally-transferred to B6 mice at day 5 post-administration of 2 mg/kg of bleomycin. Expression of active form of Srebf1 was induced by doxycycline administration at day 7 post-administration of 2 mg/kg of bleomycin. Donor cells were recovered at day 10 post--administration of 2 mg/kg of bleomycin by cell sorting. Global transcriptome of transferred fibroblasts was generated by 3'SAGE-seq using Ion Proton sequencer.
Publication Title
Transcriptome network analysis identifies protective role of the LXR/SREBP-1c axis in murine pulmonary fibrosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples