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GSE26553
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Interleukin 2 (IL-2), a cytokine linked to human autoimmune diseases, limits IL-17 production. We show that deletion of Stat3 in T cells abrogates IL-17 production and attenuates autoimmunity associated with IL-2 deficiency. While STAT3 induces IL-17 and RORt and inhibits Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and RORt. We found that STAT3 and STAT5 bound to multiple common sites across the Il17 genetic locus. The induction of STAT5 binding by IL-2 was associated with a reduction in STAT3 binding at these sites and the inhibition of associated active epigenetic marks. Titrating the relative activation of STAT3 and STAT5 modulated TH17 cell specification. Thus, the balance rather than the absolute magnitude of these signals determines the propensity of cells to make a key inflammatory cytokine.
Publication Title
Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mutations of STAT3 underlie the autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in non-hematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and non-hematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
Publication Title
A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 62 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The TALLYHO/JngJ (TH) mouse is a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. To determine the genetic factors that contribute to these T2D related characteristics in TH mice, we interbred TH mice with C57BL/6J (B6) mice. The parental, F1, and F2 mice were phenotyped at 8, 12, 16, 20, and 24 weeks of age for 4-hour fasting plasma triglyceride, cholesterol, insulin, and glucose levels, as well as body weights. Fat pad and carcass weights were measured at 24 weeks after sacrificing the mice. The F2 mice were genotyped genome-wide for 68 markers. Of 393 genotyped F2 mice, 16 were chosen from the extremes of the triglyceride distribution (8 high and 8 low), and liver, pancreas, muscle and adipose tissue were measured for gene expression. Gene expression quantitative trait locus (eQTL) analysis aided in selection of candidates underlying hyperlipidemia, diabetes and obesity QTLs. We identified several genetic loci that affected quantitative variation in plasma lipid and glucose levels and obesity traits.
Publication Title
Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 36 Downloadable Samples
Sentrix Human-6 Expression BeadChip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Neurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells; however, the intracellular mechanisms for this tumor-promoting effect are less clear. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells (LCLs) from NF1-affected and unaffected individuals.
Publication Title
Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Neurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells; however, the intracellular mechanisms for this tumor-promoting effect are less clear. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells from NF1-affected and unaffected individuals. As a cross-species filter for heterogeneity, we compared the results from two human kindreds to whole-genome transcriptional profiling in spleen-derived B-cells from age- and gender-matched Nf1+/- and wild-type mice.
Publication Title
Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Neurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells; however, the intracellular mechanisms for this tumor-promoting effect are less clear. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells (LCLs) from NF1-affected and unaffected individuals.
Publication Title
Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 77 Downloadable Samples
Illumina HiSeq 2500
Description
We use time series RNA-seq to conduct a genome-wide survey of the temporal transcriptome response of human embryonic stem (ES) cell-derived neural progenitor cells (NPCs) exposed to lead. Overall design: NPCs were derived from human embryonic stem cells (hESCs) with a modified protocol from a previously reported protocol (Chambers et al. 2009) (Methods). We used lead acetate to treat NPCs at two different concentrations, 3 µM and 30 µM.
Publication Title
RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human induced pluripotent stem (iPS) cells have previously been derived from somatic cells using viral vectors that integrate transgenes into the genome. Genomic integration, however, can allow persistent leaky expression of the transgenes and can create insertional mutations, thus limiting the utility of these cells for both research and clinical applications. Here, we describe the derivation of human iPS cells free of vector and transgene sequences using non-integrating oriP/EBNA1-based episomal vectors. The resulting iPS cells are similar to human embryonic stem (ES) cells in both proliferative and developmental potential. These results demonstrate that reprogramming of human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors, and removes one important obstacle to the clinical applications of these cells.
Publication Title
Human induced pluripotent stem cells free of vector and transgene sequences.
Sample Metadata Fields
Specimen part
View Samples