Filters
Technology
Platform
Mus musculus
7 Downloadable Samples
Illumina HiSeq 4000
Description
Regulatory T cells (Treg) are common in the tumor microenvironment in both human pancreatic cancer and in genetically engineered mouse models of the disease. Previous studies in orthotopic syngeneic models of pancreatic cancer -recapitulated in our own data- indicated that Treg depletion results CD8+ T cell-mediated tumor regression. In human patients and in mouse models, regulatory T cells accumulate during the onset of Pancreatic Intraepithelial Neoplasia (PanIN), the earliest steps of carcinogenesis. We thus generated a genetic model to investigate the role of regulatory T cells during the onset of pancreatic carcinogenesis. Unexpectedly, depletion of Tregs during early stages of carcinogenesis led to accelerated tumor progression. Overall design: We are using KC;Foxp3DTR mice generated by crossing KC (Ptf1a-Cre;LSL-KrasG12D) with Foxp3DTR (B6.129(Cg)-Foxp3tm3(DTR/GFP)Ayr/J, Jackson Laboratory). We depleted Foxp3-expressing Tregs by Diphtheria Toxin (DT) injection to determine the requirement of Tregs during oncogenic Kras induced Pancreatic Intraepithelial Neoplasia (PanIN) formation and maintenance. To investigate the mechanisms underlying the tumor-promoting effect of Treg depletion in KC; Foxp3DTR mice we performed RNA sequencing (RNAseq) for myeloid cells (DAPI-EpCAM-CD45+CD11b+) flow-sorted from KC and KC; Foxp3DTR pancreata.
Publication Title
Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2500
Description
The circadian gene expression in peripheral tissue displays rhythmicity which is driven by the circadian clock and feeding-fasting cycle in mammals. In this study, circadian transcriptome was performed to investigate how fasting influences circadian gene regulation. Overall design: 8-week-old, male C57BL/6 mice were subjected to 24-hr fasting (FAST) or to ad libitum normal chow feeding (FED) under 12hr light/ 12hr dark schedule. Liver and gastrocnemius muscle were harvested every 4 hours over the circadian cycle at ZT0, 4, 8, 12, 16, 20 (n=3 per time point per group). Total RNA was extracted from liver and gastrocnemius muscle, and used for RNA-seq.
Publication Title
Fasting Imparts a Switch to Alternative Daily Pathways in Liver and Muscle.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
Neutrophils represent a fundamental mechanism of antimicrobial resistance and inflammation 1. Moreover, neutrophils have emerged as important players in the activation, orchestration and regulation of adaptive immune responses2,3. Neutrophils are a component of the tumor microenvironment (TME) and have been prevalently shown to promote progression 4-6. On the other hand, unleashed neutrophilic effectors have also been reported to mediate anti-cancer resistance7-11. Antibody-mediated depletion used to investigate the role of neutrophils in tumor progression suffers from limitations, including duration, specificity and perturbation of the system12. We therefore used a genetic approach to investigate the role of neutrophils in primary 3-methylcholanthrene (3-MCA)-induced sarcomagenesis. Neutrophils were found to play an essential role in resistance against primary carcinogenesis by driving an interferon-? dependent type 1 immune response. Neutrophil-dependent macrophage production of IL-12p70 led to type 1 polarization of CD4- CD8- unconventional aß T cells (UTCaß) in the TME. Single cell RNAseq analysis and in vivo evidence from two preclinical sarcoma models highlight the antitumor potential of a UTCaß subset. In the TCGA cohort of human undifferentiated pleomorphic sarcomas (UPS), unlike other sarcomas, granulocyte-colony stimulating factor receptor (CSF3R) expression and a neutrophil signature were associated with better outcome and with a type 1 immune response. The positive association between high neutrophil infiltration and improved clinical outcome was confirmed in an independent UPS cohort by immunohistochemistry. Thus, neutrophils, by driving a type 1 immune response and polarization of UTCaß, mediate resistance against murine and human sarcomas. Overall design: two experimental conditions, two biological replicates for each condition
Publication Title
Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- NextSeq 500
Description
Ageing is the biggest risk factor to cardiovascular health and is associated with increased incidence of cardiovascular disease. Cellular senescence, a process driven in part by telomere shortening has been implicated in age-related cardiac dysfunction. However, the role of cellular senescence and its underlying mechanisms in slowly dividing/post-mitotic cardiomyocytes is not understood. Overall design: We quantify transcription via high throughput RNA sequencing in young (3 months) and old (20 months) mouse cardiomyocytes.
Publication Title
Length-independent telomere damage drives post-mitotic cardiomyocyte senescence.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. In order to better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profile of differentiating murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An ESC line was created that allows for the induction of Ngn3 by adding doxycycline (Dox) to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of both undifferentiated and differentiated conditions. Characterization of pancreatic developmental markers during embryoid body (EB) formation revealed an optimum context for Ngn3 induction. Neuroendocrine genes including neurogenic differentiation 1 (NeuroD1) and single minded 1 (Sim1) were found to be significantly upregulated. Genes regulated by Ngn3 independent of the context were analyzed using systematic gene ontology tools and revealed Notch signaling as the most significantly regulated signaling pathway (p=0.009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitor-mediated Notch signaling inhibition (p<0.0001). Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin transcription.
Publication Title
Differentiation of embryonic stem cells conditionally expressing neurogenin 3.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared to controls.
Publication Title
Meningeal inflammation changes the balance of TNF signalling in cortical grey matter in multiple sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We identified distict mesodermal sub-populations based on Endoglin (Eng) and Flk1 expression in Brachyury (Bry) positive cells. By using whole-transcriptome analysis, we further characterized these populations and how they changed when Wnt pathway is inhibited Overall design: Reaggregates mRNA profiles of unsorted, Flk1+ Eng+, and Flk1- Eng+ samples were generated by deep sequencing, in triplicate , using Ilumina.
Publication Title
Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
We report application of RNA-seq to quantify gene expression changes in fasted mouse livers compared to re-fed controls. Overall design: RNA-seq from livers of re-fed and 48h fasted mice.
Publication Title
Histone propionylation is a mark of active chromatin.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples
GSE2531- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In this experiment we compared total RNA from two commonly used choriocarcinoma cell lines, JEG3 and BeWo, to identify differentially expressed transcripts.
Publication Title
Microarray analysis of BeWo and JEG3 trophoblast cell lines: identification of differentially expressed transcripts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
Description
Skeletal myogenic commitment of human pluripotent cells can be achieved by doxycycline-inducible expression of the transcription factor PAX7. To gain further insights on PAX7 function during this process, we performed a time course whole transcriptome analysis of differentiating H9 human embryonic stem cells from doxycycline-treated and untreated cultures. In addition, we identified the genomic binding of PAX7 in one of the selected time point (referred as PAX7+ proliferating myogenic progenitors). Overall design: Gene expression profiling was performed on biological replicates from differentiating H9 cells at the following time points: PAX7+ mesodermal cells (day 14), PAX7+ proliferating myogenic progenitors (approximately day 23), and differentiated myocytes (differentiation stage – around day 30; 7 days in the absence of PAX7 induction). Since PAX7 expression is doxycycline inducible, we also collected uninduced control samples at the same time points (termed mesodermal cells for day 14 and proliferating cells for day 23). PAX7 genomic binding was assessed in day 23 dox-treated cultures.
Publication Title
PAX7 Targets, CD54, Integrin α9β1, and SDC2, Allow Isolation of Human ESC/iPSC-Derived Myogenic Progenitors.
Sample Metadata Fields
No sample metadata fields
View Samples