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GSE16263
Mus musculus
4 Downloadable Samples
Description
PPARg and C/EBPa cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARg and C/EBPa expression during adipogenesis remain largely unclear. Here we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARg and C/EBPa expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARg expression and PPARg-stimulated C/EBP expression. Further, PTIP is essential for induction of PPARg and C/EBPa expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARg and C/EBPa promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Furthermore, rescue of the adipogenesis defect in PTIP-/- MEFs requires co-expression of PPARg and C/EBPa. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight in mice. Thus, by regulating PPARg and C/EBPa expression, PTIP plays a critical role in adipogenesis.
Publication Title
Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha expression and adipogenesis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
Description
UTX gene is localized on the X chromosome, identified as a demethylase on histone H3 lysine 27.
Publication Title
UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
Description
A chromosomal translocation fusion gene product EWS-WT1 is the defining genetic event in Desmoplastic Small Round Cell Tumor (DSRCT), a rare but aggressive tumor with a high rate of mortality. EWS-WT1 oncogene acts as an aberrant transcription factor that drives tumorigenesis, but the mechanism by which EWS-WT1 causes tumorigenesis is not well understood. To delineate the oncogenic mechanisms, we generated the EWS-WT1 fusion in the mouse using a gene targeting (knock-in) approach, enabling physiologic expression of EWS-WT1 under the native Ews promoter. We derived mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1. Remarkably, expression of EWS-WT1 led to a dramatic induction of many neuronal genes. Notably, a neural reprogramming factor, ASCL1 (achaete-scute complex-like 1), was highly induced by EWS-WT1 in MEFs and in primary DSRCT. Further analysis demonstrated that EWS-WT1 directly binds to the proximal promoter region of ASCL1 and activates its transcription through multiple WT1-responsive elements. Depletion of EWS-WT1 in a DSRCT cell line resulted in severe reduction in ASCL1 expression and cell viability. Remarkably, when stimulated with neuronal induction media, cells expressing EWS-WT1 expressed neural markers and generated neurite-like projections. These results demonstrate for the first time that EWS-WT1 activates neural gene expression and is capable of directing partial neuronal differentiation, likely via ASCL1. These findings suggest that stimulating DSRCT tumor cells with biological or chemical agents that promote neural differentiation might be a useful approach to develop novel therapeutics against this incurable disease.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We used laser capture microdissection to isolate different zones of the articular cartilage from proximal tibiae of 1-week old mice, and used microarray to analyze global gene expression. Bioinformatic analysis corroborated previously known signaling pathways, such as Wnt and Bmp signaling, and implicated novel pathways, such as ephrin and integrin signaling, for spatially associated articular chondrocyte differentiation and proliferation. In addition, comparison of the spatial regulation of articular and growth plate cartilage revealed unexpected similarities between the superficial zone of the articular cartilage and the hypertrophic zone of the growth plate.
Publication Title
Gene expression profiling reveals similarities between the spatial architectures of postnatal articular and growth plate cartilage.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
GM-CSF controls the development of granulocytes but little is known about the contribution of the downstream mediating transcription factor STAT5A/B. To elucidate this pathway, we generated mice lacking the Stat5a and 5b genes in blood cells. Peripheral neutrophils were decreased and administration of 5-FU and GM-CSF failed to induce granulopoiesis in Stat5a/b-mutant mice. CMPs were isolated and cultured with GM-CSF.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
GM-CSF controls the development of granulocytes but little is known about the contribution of the downstream mediating transcription factor STAT5A/B. To elucidate this pathway, we generated mice lacking the Stat5a and 5b genes in blood cells. Peripheral neutrophils were decreased and administration of 5-FU and GM-CSF failed to induce granulopoiesis in Stat5a/b-mutant mice. GMPs were isolated and cultured with GM-CSF. Both the number and size of STAT5A/B-null colonies were reduced and GM-CSF-induced survival of mature STAT5A/B-null neutrophils was impaired. Time-lapse cinematography and single cell tracking of GMPs revealed that STAT5A/B-null cells were characterized by a longer generation time and an increased cell death. Gene expression profiling experiments suggested that STAT5A/B directs GM-CSF signaling through the regulation of cell survival genes.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Description
Two highly conserved transcription factors STAT5A and STAT5B play an identical role in the intracellular signaling pathway upon cytokine stimulation, while gene deletion experiments have revealed separable and overlapping functions of STAT5. This questions whether the phenotypic differences in the organ development observed in the individual knockout mice result from isoform-specific functions or quantitative differences in the expression levels of each STAT5 isoform among tissues. To elucidate the redundancy and isoform-specificity of STAT5 for development at molecular levels, mice carrying only a single allele of either Stat5a or Stat5b were generated. Both of these mice overcame the lethal anemia observed in Stat5ab-null mice, indicating that development of erythroid cell lineage was totally dependent on the dosage of STAT5. The blocked progression of B cell lineage at the pre-pro B cell stage in Stat5ab-/- mice was rescued in the presence of a single allele of either Stat5a or Stat5b, while the number of total B220+ cells in bone marrow was smaller in Stat5abnull/Stat5b- mice than Stat5abnull/Stat5a- mice. The paucity of alveolar progenitor cells in the Stat5ab-null mammary epithelium was rescued by a single allele of either Stat5a but not Stat5b, suggesting cell-type dependent isoform-specific function. Genome-wide gene expression analyses revealed that different steps of cell lineage progression require different gene sets which expression requires the different isoform of STAT5 in a dose-dependent manner in the mammary epithelium. Taken together, this study demonstrates that dose-dependent isoform specificity of STAT5A and STAT5B controls progression and differentiation of each cell lineage.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-beta/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3 deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3-/- white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3-/- adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-alpha1 expression. We observe significant correlation between TGF-beta1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-beta1 signaling protects mice from obesity, diabetes and hepatic steatosis. Together, these results demonstrate that TGF-beta signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-beta1 activity might be an effective treatment strategy for obesity and diabetes.
Publication Title
Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Description
Stat5+/- mice were bred into the C57BL/6 background. Stat5+/- mice were intercrossed and mouse embryonic fibroblasts (MEFs) were isolated from 12.5-13.5-day WT or Stat5-/- fetuses. The retroviral-expression vector carrying a wild-type Stat5A gene based on an MSCV-IRES-GFP backbone (gift from Richard Moriggl, Ludwig-Boltzmann Institute, Vienna, Austria) was infected into Stat5-/- MEFs. FACS was used to select GFP+ cells. After 5 hours starvation in serum free medium with 0.1% of BSA, MEFs were treated with growth hormone for 2 hours. Total cellular RNA from each group of the MEFs was extracted with TRIzol reagent (Invitrogen) according to the manufacturer's instructions. Microarray analyses were performed using Affymetrix Mouse Genome 430 2.0 GeneChips (Affymetrix, Santa Clara, CA) (six groups, biological replicates for each group). Expression values were determined with GeneChip Operating Software (GCOS) v1.1.1 software. RMA signals were summarized using GeneSpring GX 10.0.1 (Agilent) and normalized by quantile normalization. All data analysis was performed with GeneSpring software GX 10.01.
Publication Title
Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes.
Sample Metadata Fields
Specimen part
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