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Mus musculus
16 Downloadable Samples
VUmc/Illumina Sentrix MouseRef8 v1.1
Description
Breast cancer cells facilitate distant metastasis through the induction of immunosuppressive regulatory B cells, designated tBregs. We report here that, to do this, breast cancer cells produce metabolites of the 5-lipoxygenase (5-LO) pathway such as leukotriene B4 (LTB4) to activate the proliferator-activated receptor alpha (PPARalpha) in B cells. Inactivation of LTB4 signaling or genetic deficiency of PPARalpha in B cells blocks the generation of tBregs and thereby abrogates lung metastasis in mice with established breast cancer. Thus, in addition to eliciting fatty acid oxidation and metabolic signals, PPARalpha initiates programs required for differentiation of tBregs. We propose that PPARalpha in B cells or/and tumor 5-LO pathways represents new targets for pharmacological control of tBreg-mediated cancer escape.
Publication Title
Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked regulatory B cells via peroxisome proliferator-activated receptor α.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demonstrated that a dominant mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrheic dermatitis. We defined ZNF750 as a nuclear effector that is strongly activated in and essential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differentiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier
Publication Title
ZNF750 is expressed in differentiated keratinocytes and regulates epidermal late differentiation genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The Ets transcription factor, ERG, plays a central role in definitive hematopoiesis and its overexpression in acute myeloid leukemia is associated with a stem cell signature and bad prognosis. However, little is known about the underlying mechanism by which ERG causes leukemia. Therefore we sought to identify ERG targets that participate in development of leukemia by integration of expression arrays and Chromatin immunoprecipitation.
Publication Title
Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
An understanding of the mechanisms regulating white adipose tissue (WAT) formation is key for developing of new tools to treat obesity and its related diseases. Here, we identify DEPTOR as a positive regulator of adipogenesis whose expression is associated with obesity. In a polygenic mouse model of obesity/leanness, Deptor is part of the Fob3a QTL linked to obesity and we fine that Deptor is the highest priority candidate gene regulating WAT accumulation in this model. Using a doxycycline-inducible mouse model for Deptor overexpression, we confirmed that Deptor promotes WAT expansion in vivo. DEPTOR expression is elevated in WAT of obese humans and strongly correlates with the degree of obesity. We show that DEPTOR is induced during adipogenesis and that its overexpression cell-autonomously promotes, while its suppression blocks, adipogenesis. DEPTOR positively regulates adipogenesis by promoting the activity of the pro-adipogenic factors Akt/PKB and PPAR-gamma. These results establish DEPTOR as a physiological regulator of adipogenesis and provide new insights into the molecular mechanisms controlling WAT formation.
Publication Title
DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Ob/ob mice were given 0, 12.5 or 25 ng/hr leptin through an osmotic pump. After 12 days, livers RNA was prepared and illumina microarrays were done. We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma [glucose] and [insulin]. We found that a leptin dose of 12.5 ng/hour significantly lowers blood glucose and that 25 ng/hour of leptin normalizes plasma glucose and insulin without significantly reducing body weight, thus establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 as being regulated by leptin with a similarly high potency. Over-expression of IGFBP2 by an adenovirus reversed diabetes in insulin resistant ob/ob, Ay/a and diet-induced obese mice (DIO), as well as insulin deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a three-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment in ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.
Publication Title
Antidiabetic effects of IGFBP2, a leptin-regulated gene.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The goal of this study was to identify genes which are differentiatlly expresesd upon induced inactivation of Rfx6 in beta cell in adult mice Overall design: Rfx6fl/fl; Ins1-CreERT2 (mut) and Rfx6fl/fl (ctrl) 8 weeks old mice were injected subcutaneously with tamoxifen daily during 3 days. Pancreatic islets were isolated 5 days after the first injection and RNA purified.
Publication Title
Rfx6 maintains the functional identity of adult pancreatic β cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We report that phosphorylated ribosomes can be immunoprecipitated from mouse brain homogenates, resulting in enrichment of transcripts expressed in activated neurons. Overall design: Mice were either injected with a concentrated salt solution or vehicle, hypothalami dissected, and phosphorylated ribosomes immunoprecipitated. RNA was sequenced from the input and IP for each condition (4 samples total).
Publication Title
Molecular profiling of activated neurons by phosphorylated ribosome capture.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 134 Downloadable Samples
- NextSeq 500
Description
Cellular function is strongly dependent on surrounding cells and environmental factors. Current technologies are limited in characterizing the spatial location and unique gene-programs of cells in less structured and dynamic niches. Here we developed a method (NICHE-seq) that combines photoactivatable fluorescent reporters, two-photon microscopy and single-cell RNA-seq to infer the cellular and molecular composition of niches. We applied NICHE-seq to examine the high-order assembly of immune cell networks. NICHE-seq is highly reproducible in spatial tissue reconstruction, enabling identification of rare niche-specific immune subpopulations and unique gene-programs, including natural killer cells within infected B cell follicles and distinct myeloid states in the marginal zone. This study establishes NICHE-seq as a broadly applicable method for elucidating high-order spatial organization of cell types and their molecular pathways. Overall design: Transcriptional profiling of single cells from the specific immune niches in the lymph node and spleen, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500
Publication Title
Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples
GSE26906- Homo sapiens
- 90 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of expression profiles in stage II colon cancer according to the APC gene status
Publication Title
Expression Profiles in Stage II Colon Cancer According to APC Gene Status.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
The 16p11.2 deletion and duplication syndromes have been associated with developmental delay and autism spectrum disorders, and a reciprocal effect on body mass index. Here we explored these links with new engineered mouse models carrying a deletion (Del/+) and duplication (Dup/+) of the whole 16p11.2 homologous Sult1a1-Spn region. On a pure genetic background, compared to wild-types, Del/+ mice carrying the deletion showed weight and adipogenesis deficits, hyperactivity, repetitive behaviors, and recognition memory deficits, whereas Dup/+ mice showed the opposite phenotypes and Del/Dup individuals displayed no changes. Alterations in social interaction were also observed in Del/+ and Dup/+ animals on a mixed genetic background.
Publication Title
Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.
Sample Metadata Fields
Sex, Specimen part
View Samples