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SRP340816
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
Barrier integrity is central to the maintenance of a healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic diseases such as food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD, we report that a fermentable fibre-rich diet alleviates AD severity and systemic allergen sensitization. The gut-skin axis underpins this phenomenon through SCFA, which strengthen skin barrier integrity by altering mitochondrial metabolism of epidermal keratinocytes. SCFA promote keratinocyte differentiation and the production of key structural lipids, resulting in enhanced barrier function. Our results demonstrate that dietary fibre and SCFA mitigate AD by improving barrier integrity, ultimately limiting early systemic allergen sensitization and development of disease. Overall design: 16 Samples, 4 groups in duplicate
Publication Title
Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation.
Sample Metadata Fields
Genotype, Disease, Disease stage, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Breast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis-free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2r-/- mice), we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases.
Publication Title
Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Transcriptional events during initial vertebrate heart development in vivo remain poorly understood. Mesp1, a bHLH transcription factor, has been described as the earliest transcriptional regulator of cardiac progenitors in multiple species, and represents an excellent candidate for the investigation of relevant targets during cardiovascular development. We report here that both depletion and mutation of Mespaa, the zebrafish homolog of mammalian Mesp1, lead to randomization of cardiac looping, together with significant cardiac morphogenesis defects. These disruptions are preceded by a defect in cardiac left-right asymmetry. Surprisingly, the defect in asymmetry was found to occur independently of defects in the transient organ of laterality, the Kupffer’s vesicle (KV). We show that Mespaa regulates miR-430 expression during gastrulation to control the levels of Nodal signaling, and that this regulation is required for asymmetric laterality signaling in the prospective heart field. Ectopic expression of miR-430 is sufficient to induce cardiac laterality defects, and consistent with Mespaa over-expression in this system, the reduction of miR-430 leads to cardia bifida. This study reveals a novel transcriptional regulation of miR-430 by Mespaa and a role for this pathway in cardiac laterality during gastrulation.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
To test the regulatory effects of Dmrt5 on gene expression, we designed tetracycline inducible lines of Dmrt5 transgenic mouse ESCs. Overexpression of Dmrt5 was induced upon addition of Doxycycline (Dox). To evaluate the effects of Dmrt5 on gene expression in different stages of in vitro differentiated NPC derived from mouse embryonic stem cells (ESC), we analyzed gene expression profiles at differentiation day 7 and day 9 with or without Dox. The data revealed that overexpression of Dmrt5 in in vitro differentiated neural progenitor cells (NPC) regulates gene expression. Addition of Dox to the medium of the control cell line rtTA did not significantly alter gene expression profile, demonstrating that the observed effects were through induction of Dmrt5, but not simply through Dox.
Publication Title
Doublesex and mab-3-related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The data revealed differential expression between floor plate and ventral lateral region in E10.5 mouse embryo midbrain. Several differentially expressed genes in these regions have been reported in the literature, demonstrating reliability of tissue dissection.
Publication Title
No associated publication
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We assessed the impact of glucose transporter Glut2 gene inactivation in adult mouse liver (LG2KO mice). This suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was normal early after Glut2 inactivation but intolerance developed at later time. This was caused by progressive impairment of glucose-stimulated insulin secretion even though beta-cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinate down-regulation of cholesterol biosynthesis genes in LG2KO mice. This was associated with reduced hepatic cholesterol in fasted mice and a 30 percent reduction in bile acid production. We showed that chronic bile acids or FXR agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls beta-cell glucose competence, through a mechanism that likely depends on bile acid production and action on beta-cells.
Publication Title
Hepatic glucose sensing is required to preserve β cell glucose competence.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina NovaSeq 6000
Description
Cigarette smoke (CS) is one of risk factor to chronic obstructive pulmonary disease that is the major causes of death in the world. Furthermore, CS is an independent risk factor for chronic kidney disease (CKD) in the general adult population. The goal of this project was to identified the mechanisms of renal damage that might be associated with exposure to CS extract (CSE) in human kidney proximal tubular epithelial cell line (HK-2 cells) cells. Overall design: RNA sequencing of human kidney proximal tubular epithelial cell line (HK-2 cells) after 24 hours exposure to 0.6% CSE.
Publication Title
Cigarette Smoke Exposure Increases Glucose-6-phosphate Dehydrogenase, Autophagy, Fibrosis, and Senescence in Kidney Cells In Vitro and In Vivo.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Background and Aims: In the interleukin-10-deficient (Il10-/-) mouse model of IBD, 10 quantitative trait loci (QTL) have been shown to be associated with colitis susceptibility by linkage analyses on experimental crosses of highly susceptible C3H/HeJBir (C3Bir)-Il10-/- and partially resistant C57BL/6J (B6)-Il10-/- mice. The strongest locus (C3Bir-derived cytokine deficiency-induced colitis susceptibility [Cdcs]1 on Chromosome [Chr] 3) controlled multiple colitogenic subphenotypes and contributed the vast majority to the phenotypic variance in cecum and colon. This was demonstrated by interval-specific Chr 3 congenic mice wherein defined regions of Cdcs1 from C3Bir or B6 were bred into the IL-10-deficient reciprocal background and altered the susceptible or resistant phenotype. Furthermore, this locus likely acts by inducing innate hypo- and adaptive hyperresponsiveness, associated with impaired NFB responses of macrophages. The aim of the present study was to dissect the complexity of Cdcs1 by further development and characterization of reciprocal Cdcs1 congenic strains and to identify potential candidate genes in the congenic interval. Material and Methods: In total, 15 reciprocal congenic strains were generated from Il10-/- mice of either C3H/HeJBir or C57BL/6J backgrounds by 10 cycles of backcrossing. Colitis activity was monitored by histological grading. Candidate genes were identified by fine mapping of congenic intervals, sequencing, microarray analysis and a high-throughput real-time RT-PCR approach using bone marrow-derived macrophages. Results: Within the originally identified Cdcs1-interval, three independent regions were detected that likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression differences between susceptible and resistant mouse strains. Conclusions: Subcongenic analysis of the major susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic structure. Candidate gene approaches revealed attractive genes within the identified regions with homologs that are located in human susceptibility regions for IBD.
Publication Title
Cdcs1 a major colitis susceptibility locus in mice; subcongenic analysis reveals genetic complexity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Extraembryonic trophoblast stem cells (TSC) can be converted to induced pluripotent stem cells (TSC-iPSCs) by overexpressing Oct4, Sox2, Klf4 and cMyc.
Publication Title
Lineage conversion of murine extraembryonic trophoblast stem cells to pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
Description
Germ free (GF) and conventionalized (CONV-D) wild-type C57Bl/6 male mice in the CARB-fed, 24h fasted, and 30d trained states; plus GF and CONV-D CARB-fed Ppara-/- mice. CARB-fed indicates a standard polysaccharide-rich mouse chow diet.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples