Filters
Technology
Platform
GSE25645
Mus musculus
16 Downloadable Samples
Description
STAT5 is critical for differentiation, proliferation and survival of progenitor B cells suggesting a possible role in Acute Lymphoblastic Leukemia (ALL). Herein, we show increased expression of activated STAT5 in ALL patients, which correlates with treatment outcome. Mutations in Ebf1 and Pax5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1 but this had little affect on most EBF1 or PAX5 target genes. However, a subset of these genes was deregulated and included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL.
Publication Title
Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 33 Downloadable Samples
Description
The transcription factor STAT5 plays a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we demonstrate that STAT5 activation cooperates with defects in the pre-BCR signaling components encoded by Blnk, Btk, Prkcb, Nfkb1, and Ikzf1 to initiate B-ALL. STAT5 antagonizes NF-B and IKAROS by opposing regulation of shared target genes. STAT5 binding was enriched at super-enhancers, which were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4, and IKAROS. Patients with high ratios of active STAT5 to NF-B or IKAROS have more aggressive disease. Our studies illustrate that an imbalance of two opposing transcriptional programs drive B-ALL, and suggest that restoring the balance of these pathways may inhibit B-ALL.
Publication Title
Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The objective of this set of samples is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by ionizing radiation in wild-type murine pre-B cells. The data generated in this project will be compared to the data generated in GSE9024, in which genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells were examined. In order to understand the differences between the physiologic and genotoxic responses to DSB DNA damage, we need to compare cells that are all in the same compartment of the cell cycle. We are therefore examining the response to IR-induced damage in cells that are arrested in G1, which would correspond to our previous study of G1 arrested cells with Rag-induced breaks. This will illuminate the difference directly, allowing us to better understand the signaling responses to the different types of DNA damage.
Publication Title
DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
Description
The mature CNS contains PDGFRA+ oligodendrocyte progenitor cells (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence.
Publication Title
Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin
Publication Title
Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Targeted disruption of Hotair leads to homeotic transformation and gene derepression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Long noncoding RNAs (lncRNAs) are thought to be prevalent regulators of gene expression, but the consequences of lncRNA inactivation in vivo are mostly unknown. Here we show that targeted deletion of mouse Hotair lncRNA leads to de-repression of hundreds of genes, resulting in homeotic transformation of the spine and malformation of metacarpal-carpal bones. RNA-seq and conditional inactivation reveal an ongoing requirement of Hotair to repress HoxD genes and multiple imprinted loci such as Dlk1-Meg3 and Igf2-H19. Hotair binds to both Polycomb repressive complex 2 that methylates histone H3 at lysine 27 (H3K27) and Lsd1 complex that demethylates histone H3 at lysine 4 (H3K4) in vivo. Hotair inactivation causes coordinate H3K27me3 loss and H3K4me3 gain at select target genes throughout the genome. These results reveal a shared regulatory mechanism to enforce silent chromatin state at Hox and imprinted genes via Hotair lncRNA.
Publication Title
Targeted disruption of Hotair leads to homeotic transformation and gene derepression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
Description
Exercise training improves whole body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues including adipose tissue. To determine if exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, nine days post-transplantation, mice receiving trained scWAT had improved glucose tolerance and enhanced insulin sensitivity compared to mice transplanted with sedentary scWAT or sham-treated mice. Mice transplanted with trained scWAT had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat fed recipient mice were transplanted with trained scWAT. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT including increased expression of 1550 genes involved in numerous cellular functions, including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis.
Publication Title
A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
We have identified a population of adipocytes in fat tissue that arise from bone marrow-derived progenitor cells.
Publication Title
De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
The ACBP knockout were created by targeted disruption of the gene in mice. The expression profiling was performed on liver tissue from ACBP-/- (KO) and +/+ (WT) mice at the age of 21 days, which in our study is the time immediately before weaning. The mice used for this experiment were taken directly away from their mother. Thus, having free access to chow and breast milk until sacrificed at 8-11am
Publication Title
Disruption of the acyl-CoA-binding protein gene delays hepatic adaptation to metabolic changes at weaning.
Sample Metadata Fields
Specimen part
View Samples