Filters
Technology
Platform
GSE12038
Mus musculus
2 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
XBP1 is the transcriptino factor that is activated by the ER stress. XBP1 is known to induce the ER dexpansion and increase the expression of the ER chaperone genes to prtect the cell from the ER stress. We generated a mouse strain that lacked XBP1 specifically in the mouse intestine by breeding the XBP1flox mice with Villin-cre mice. Here we examined genes that are differentially expressed between WT and XBP1 KO mouse intestine to identify genes that are downstream of XBP1.
Publication Title
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cell based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life which can differentiate to remodel or repair the fractured bone. However, cell based skeletal repair in the clinic is still in its infancy mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here we took a combined approach of high throughput screening, flow based cell sorting and in vivo transplantation to identify markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105+vemesenchymal cells and these cells readily form bone upon transplantation. In addition we have used Thy1.2 (CD90) and the ectonucleotidase CD73 to identify subsets within the CD9+ve population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties.
Publication Title
Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor population with elevated osteogenic properties.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiScanSQ
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Increased DNA methylation of Dnmt3b targets impairs leukemogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiScanSQ
Description
Here, we analyzed global gene expression changes that were associated with over expression of Dnmt3b in MLL-AF9 induced leukemias using the Affymetrix microarray platform.
Publication Title
Increased DNA methylation of Dnmt3b targets impairs leukemogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec). Similarly, inducible expression of EVI1 in HL-60 cells decreased their sensitivity to daunorubicin. Gene expression microarray analyses of U937_EVI1 and U937_vec cells cultured in the absence or presence of etoposide showed that 77 and 419 genes were regulated by EVI1 and etoposide, respectively. Notably, mRNA levels of 26 of these genes were altered by both stimuli, indicating that EVI1 regulated genes were strongly enriched among etoposide regulated genes and vice versa. One of the genes that were induced by both EVI1 and etoposide was CDKN1A/p21/WAF, which in addition to its function as a cell cycle regulator plays an important role in conferring chemotherapy resistance in various tumor types. Indeed, overexpression of CDKN1A in U937 cells mimicked the phenotype of EVI1 overexpression, similarly conferring partial resistance to antileukemic drugs.
Publication Title
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The goals of this study are to assess the transcriptional networks governed by the transcription factor XBP1 in lineage-uncommitted myeloid progenitors and in eosinophil-committed myeloid progenitors. Methods: mRNA profiles of FACS-purified granulocyte-macrophage progenitors (GMPs) from XBP1 flox/flox or XBP1 flox/flox Vav1-Cre mice were generated by sequencing, in biological triplicates, using an Illumina HiSeq2000 sequencer. The Illumina HiSeq2000 sequencer was also used to obtain mRNA profiles of FACS-purified GMPs transduced with the transcription factor GATA2, resorted 36 hours post-transduction, and cultured for 48 hours, again in biological triplicates per genotype. Sequence data from Illumina''s HiSeq2000 sequencer were demuxed to generate FASTQ files for each sample using Illumina''s CASAVA pipeline (version 1.8.2). The reads that passed illumina''s quality/purity filter were aligned to the mouse genome (Illumina iGenomes mm9 build) using STAR aligner (version 2.3.0) with default parameters. The resulting SAM alignment files were then converted to the BAM file format, sorted and indexed using SAMtools (version 0.1.14). Mapped reads were counted with the python module HTSeq, and differential expression analyzed with the Bioconductor package DESeq. Results and conclusions: By monitoring XBP1-dependent transcriptional changes at different stages of eosinophil development, we demonstrated that classical XBP1-dependent networks such as glycosylation, chaperone production, and ERAD were downregulated in GMPs prior to eosinophil commitment, though there were no major defects in differentiation or survival. However, mRNA profiling clearly demonstrated that XBP1 deficiency causes a state of cellular stress upon eosinophil commitment. The eosinophil transcriptome was largely intact, and most dysregulated genes were associated with ER stress. However key granule protein genes required for eosinophil development such as Prg2 and Epx were selectively downregulated only after eosinophil commitment, but not in pre-committed myeloid progenitors, and this correlated with Ingenuity Pathway Analysis predictions that GATA1 function was impaired. This study documents the interplay between cellular stress and the ability to maintain key facets of cellular differentiation. Overall design: Analyses of XBP1-dependent transcriptional networks at two stages of eosinophil development.
Publication Title
The transcription factor XBP1 is selectively required for eosinophil differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Genetic deletion of Nfatc1 in mice results in profound osteoclast-poor osteopetrosis, a high bone mass state caused by a lack of osteoclast activity. We hypothesized that the family of NFATc1 regulated transcripts in the osteoclast would be enriched for genes associated with osteoclast function. We used microarrays profile gene expression in wild-type and NFATc1-deficient osteoclasts generated in vitro to identify NFATc1-dependent transcripts in osteoclasts.
Publication Title
NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Here we report that the transcription factor cyclic AMPresponsive elementbinding protein H (CREB-H, encoded by CREB3L3) is required for the maintenance of normal plasma triglyceride concentrations. CREB-Hdeficient mice showed hypertriglyceridemia secondary to inefficient triglyceride clearance catalyzed by lipoprotein lipase (Lpl), partly due to defective expression of the Lpl coactivators Apoc2, Apoa4 and Apoa5 and concurrent augmentation of the Lpl inhibitor Apoc3. We identified multiple nonsynonymous mutations in CREB3L3 that produced hypomorphic or nonfunctional CREB-H protein in humans with extreme hypertriglyceridemia, implying a crucial role for CREB-H in human triglyceride metabolism.
Publication Title
The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+ CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg transcriptional signature. Computational network inference and experimental testing assessed the contribution of several other transcription factors (TFs). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability.
Publication Title
A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples