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GSE49894
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
In all primary cells analyzed to date, aneuploidy is associated with poor proliferation. Yet, how abnormal karyotypes affect cancer a disease characterized by both aneuploidy and heightened proliferative capacity is largely unknown. Here, I demonstrate that the transcriptional alterations caused by aneuploidy in primary cells are also present in chromosomally-unstable cancer cell lines, but are not common to all aneuploid cancers. Moreover, chromosomally-unstable cancer lines display increased glycolytic and TCA-cycle flux, as is also observed in primary aneuploid cells. The biological response to aneuploidy is associated with cellular stress and slow proliferation, and a 70-gene signature derived from primary aneuploid cells is a strong predictor of increased survival in several cancers. Inversely, a transcriptional signature derived from clonal aneuploidy in tumors correlates with high mitotic activity and poor prognosis. I speculate that there are two types of aneuploidy in cancer: clonal aneuploidy, which is selected during tumor evolution and is associated with robust growth, and sub-clonal aneuploidy, which is caused by chromosomal instability (CIN) and more closely resembles the stressed state of primary aneuploid cells. Nonetheless, CIN is not benign: a subset of genes upregulated in high-CIN cancers predict aggressive disease in human patients in a proliferation-independent manner.
Publication Title
A transcriptional and metabolic signature of primary aneuploidy is present in chromosomally unstable cancer cells and informs clinical prognosis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mesothelia, which cover all coelomic organs and body cavities in vertebrates, perform diverse functions in embryonic and adult life. Yet, mesothelia are traditionally viewed as simple, uniform epithelia.
Publication Title
Autotaxin signaling governs phenotypic heterogeneity in visceral and parietal mesothelia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC. Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.
Publication Title
Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Skeletal muscle possesses remarkable regenerative potential due to satellite cells, a stem cell population located beneath the muscle basal lamina. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a unique myogenic lineage that resides outside the basal lamina of adult muscle and contributes specifically to type IIb/x myofibers during adulthood and muscle regeneration. Tw2+ progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro and can fuse with satellite cells. Transplantation of Tw2+ progenitors into adult mice is sufficient to reconstitute new myofibers, and genetic ablation of endogenous Tw2+ progenitors causes wasting of type IIb myofibers. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that suppress Tw2 expression. Tw2-expressing progenitors represent a previously unrecognized, fiber-type specific progenitor cell involved in muscle growth and regeneration. Overall design: Gene expression profile was generated by comparing freshly sorted Twist2+ and Pax7+ cells from skeletal muscle
Publication Title
A Twist2-dependent progenitor cell contributes to adult skeletal muscle.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Skeletal muscle possesses remarkable regenerative potential due to satellite cells, a stem cell population located beneath the muscle basal lamina. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a unique myogenic lineage that resides outside the basal lamina of adult muscle and contributes specifically to type IIb/x myofibers during adulthood and muscle regeneration. Tw2+ progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro and can fuse with satellite cells. Transplantation of Tw2+ progenitors into adult mice is sufficient to reconstitute new myofibers, and genetic ablation of endogenous Tw2+ progenitors causes wasting of type IIb myofibers. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that suppress Tw2 expression. Tw2-expressing progenitors represent a previously unrecognized, fiber-type specific progenitor cell involved in muscle growth and regeneration. Overall design: Gene expression profile was generated by comparing Twist2- or GFP-overexpressing Tw2 myoblasts before and after differentiation.
Publication Title
A Twist2-dependent progenitor cell contributes to adult skeletal muscle.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life.
Publication Title
Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Decreased bile secretion in rodents by either ligation of the common bile duct or induction of cirrhosis causes changes in the small intestine, including bacterial overgrowth and translocation across the mucosal barrier. Oral administration of bile acids inhibits these effects. The genes regulated by FXR in ileum suggested that it might contribute to the enteroprotective actions of bile acids. To test this hypothesis, mice were administered either GW4064 or vehicle for 2 days and then subjected to bile duct ligation (BDL) or sham operation. After 5 days, during which GW4064 or vehicle treatment was continued, the mice were killed and their intestines were analyzed for FXR target gene expression.
Publication Title
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Obstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier. These findings reveal a central role for FXR in protecting the distal small intestine from bacterial invasion and suggest that FXR agonists may prevent epithelial deterioration and bacterial translocation in patients with impaired bile flow. In this report we have examined the role of FXR in the ileum. We demonstrate that it plays a crucial role in preventing bacterial overgrowth and maintaining the integrity of the intestinal epithelium
Publication Title
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor.
Sample Metadata Fields
Sex, Compound
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hexose-6-phosphate dehydrogenase (H6PD)is the initial component of a pentose phosphate pathway inside the endoplasmic reticulum (ER) that generates NADPH for ER enzymes. In liver, H6PD is required for the 11-oxoreductase activity of 11ss-hydroxysteroid dehydrogenase type 1 (11ss-HSD1), which converts inactive 11-oxo glucocorticoids to their active 11-hydroxyl counterparts; consequently, H6PD null mice are relatively insensitive to glucocorticoids, exhibiting fasting hypoglycemia, increased insulin sensitivity despite elevated circulating levels of corticosterone, and increased basal and insulin-stimulated glucose uptake in muscles normally enriched in Type II (fast) fibers which have increased glycogen content. They also display a progressive vacuolar myopathy evident after 4 weeks of age.
Publication Title
Deletion of hexose-6-phosphate dehydrogenase activates the unfolded protein response pathway and induces skeletal myopathy.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have isolated cells from the B16F10 melanoma cell line which express the vascular-selective marker PECAM1
Publication Title
Vascular channels formed by subpopulations of PECAM1+ melanoma cells.
Sample Metadata Fields
Cell line
View Samples