Filters
Technology
Platform
SRP056698
Saccharomyces cerevisiae
12 Downloadable Samples
Illumina HiSeq 2500
Description
Nuclear pore complexes (NPCs) influence gene expression besides their established function in nuclear transport. The TREX-2 complex localizes to the NPC basket and affects gene-NPC interactions, transcription and mRNA export. How TREX-2 regulates the gene expression machinery is unknown. Here, we show that TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II. Structural and biochemical studies identify a conserved region on TREX-2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates assembly of Mediator with its Cdk8 kinase and is required for recruitment and site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling confirm that TREX-2 and Med31 are functionally interdependent. TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing at the Mediator level. In sum, we provide insight into how NPC-associated adaptor complexes can access the core transcription machinery. Overall design: RNAseq was performed from WT, sac3?, cdk8? and Sac3 R288D mutant cells. For each strain triplicates were analyzed. WT strain was sac3? transformed with pRS315 SAC3 WT
Publication Title
The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 18 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and highly active in the epidermis. AhR-ligands can accelerate keratinocyte differentiation, but a precise role for AhR in the skin barrier is unknown. We here show that transepidermal water loss (TEWL), a parameter of skin barrier integrity, is high in AhR-deficient (AhR-KO) mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the major responsible cell population for high TEWL. Electron microscopy showed weaker inter-cellular connectivity in the epidermis of keratinocytes in AhR-KO mice, and gene expression analysis identified many barrier-associated genes as AhR targets. Moreover, AhR-deficient mice had higher inter-individual differences in their microbiome. Interestingly, removing AhR-ligands from the diet of wild-type mice mimicked AhR-deficiency regarding the impaired barrier. Vice versa, re-addition of the plant-derived ligand indole-3-carbinol (I3C) rescued the barrier deficiency even in aged mice. Our results suggest that functional AhR expression is critical for skin barrier integrity and that AhR represents a molecular target for the development of novel therapeutic approaches for skin barrier diseases, including dietary intervention.
Publication Title
Aryl Hydrocarbon Receptor in Keratinocytes Is Essential for Murine Skin Barrier Integrity.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 27 Downloadable Samples
- NextSeq 500
Description
Characterization of different astrocytes soruces was done using RNAseq including samples from human primary adult brain, astrocytoma, and hiPSC derived astrocytes including neural stem cell origin Overall design: Full RNAseq (>200nt) of biological triplicates isolated with Illumina TrueSeq Stranded mRNA LT Sample Prep Kit and sequenced using Illumina NextSeq 500 sequencer
Publication Title
Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- NextSeq 500
Description
Fine control of macrophage activation is required to prevent inflammatory disease, particularly at barrier sites such as the lung. However, the dominant mechanisms that regulate pulmonary MFs during inflammation are currently poorly understood. Here we show that airway MFs are substantially less able to respond to the canonical type-2 cytokine IL-4, which underpins allergic disease and parasite worm infections, than lung tissue or peritoneal cavity MFs. We reveal that MF hypo-responsiveness to IL-4 is dictated by the lung environment, though independent of the host microbiota or the prominent lung extracellular matrix components surfactant protein D and mucin 5b. Rather, compared to cavity MFs, airway MFs display severely dysregulated metabolism. Strikingly, upon removal from the lung, alveolar MFs regain IL-4 responsiveness in a process dependent upon glycolysis. Thus, we propose that impaired glycolysis within the pulmonary niche is a central determinant for regulation of MF responsiveness during type-2 inflammation. Overall design: The 13 analysed samples belong to 6 different groups, each group consisted of 2 or 3 samples. The groups consist of 3 separate macrophage populations, from either control or IL-4 complex treated mice. Each individual sample was generated from 3-5 pooled biological replicate mice.
Publication Title
The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
- NextSeq 500
Description
We report RNA Seq analysis using Illumina nextSeq500 of human beta cells EndoC-BH1 treated with FGF2 to induce dedifferentiation. FGF2 treatment induced dedifferentiation of EndoC-BH1 cells. Indeed, we observed a strong decrease in expression of ß-cell markers, (INS, MAFB, SLC2A2, SLC30A8 and GCK). Opposingly, we identifed positive markers of human ß cell dedifferentiation, as attested by increased expression of mature ß-cell disallowed transcription factors (MYC, HES1, SOX9 and NEUROG3). Interestingly, our temporal analysis revealed that loss of expression of ß cell specific markers preceded the induction of ß cell disallowed genes. Overall design: human beta cells EndoC-BH1 were treated with FGF2 (100ng/L) during 4, 24, 72 and 144h. RNA was isolated post treatment, along with the non-treated controls, and RNA Seq was performed using Illumina nextSeq500 to generate a full transcriptome analysis of gene expression during dedifferentiation of pancreatic beta cells.
Publication Title
Modeling human pancreatic beta cell dedifferentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD103+CD11b+ dendritic cells (DC) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGF beta 1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103CD11b+ DC subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1fl/fl mice reflects defective differentiation from CD103CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T (Treg) cells in vitro and in vivo, and by reduced numbers of endogenous TH17 cells in the intestinal mucosa. Thus, TGF beta 1 mediated signalling may explain the tissue-specific development of these unique DCs.
Publication Title
TGFβR signalling controls CD103<sup>+</sup>CD11b<sup>+</sup> dendritic cell development in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Examine gene expression for meningioma cases by hormone receptor status and indicate a stronger association with progesterone than with estrogen receptors
Publication Title
Specific genes expressed in association with progesterone receptors in meningioma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 111 Downloadable Samples
- NextSeq 500
Description
Purpose: To investigate alterations in subcutaneous white adipose gene expression induced by genetic AMPK activation in vivo, in mice fed a chow or a high-fat diet. Methods: Subcutaneous white adipose tissue mRNA profiles of wild-type transgenic (WT-Tg) mice and mice expressing a gain-of-function AMPK mutant gamma1 subunit (D316A-Tg) were generated by deep sequencing. Results: RNA sequencing revealed over 3000 differentially expressed genes between WT-Tg and D316A-Tg subcutaneous white adipose tissue (WATsc) from mice fed a high fat diet (HFD), of which many were classified as 'skeletal muscle-associated'. Interestingly, uncoupling protein 1 (UCP1), associated with 'beige' adipocyte formation in WATsc, was not differentially expressed. On a chow diet, many differentially expressed genes were also identified, with gene ontology analysis identifiying glycolysis, TCA cycle and brown fat differentiation as highly enriched; key features of brown adipocyte identity. HFD-associated skeletal-muscle associated gene expression was either not significantly altered, or significantly down-regulated on a chow diet, indicating a diet-induced gene signature in D316A-Tg WATsc. Conclusions: Our study revealed gene signatures indicative of brown adipocyte development on a chow diet, where no overt metabolic phenotype was observed in gain-of-function animals. When fed a HFD, WATsc from D316A-Tg mice displayed a muscle-like gene signature, expressing key components of creatine and calcium thermogenic cycles including Ckmt2 (creatine kinase, mitochondrial 2) Atp2a1 (SERCA1-sarco/endoplasmic reticulum ATPase 1) and ryr1 (ryanodine receptor 1). UCP1 expression was not altered between WT-Tg and D316A-Tg mice fed a HFD. Our findings suggest a novel role for AMPK in the regulation of white adipocyte identity and a potentially novel cell population that, when metabolically challenged, preferrentially utilise muscle-like thermogenic futile cycles independent of UCP1 to mediate whole organism energy expenditure. Overall design: Whole subcutaneous white adipose tissue mRNA profiles were generated from mice fed either chow or 45% high-fat diet.
Publication Title
AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Atopic dermatitis and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. We show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of atopic dermatitis-specific Th2 and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in atopic dermatitis, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naïve mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in atopic dermatitis and psoriasis. Overall design: Eight- to 12-week old male mice were used. TWEAK-deficient animals were bred in house on the C57BL/6 background, and Fn14-deficient animals on a BALB/c. Atopic Dermatitis-like disease was induced by epicutaneous treatment with HDM extract (10 µg/mouse and treatment) and SEB (500 ng/mouse and treatment) given in 2 cycles on days 1 and 4, and 14 and 17, on the shaved and tape-stripped back skin over a 23 day period.
Publication Title
TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
B6D2F1 male mice at the age of 6 weeks were maintained for one week in a 12h light / 12 h dark (LD12:12) cycle (lights on from 7:00 am to 7:00 pm) and food and water ad libitum. Mice were then divided in two experimental groups which were further maintained for 3 weeks in the LD12 cycle and fed either at libitum or only during a 4 h period between 9:00 am and 1:00 pm. All animals were then implanted subcutaneously with a pancreatic P03 adenocarcinoma in both flanks. Tumour growth was monitored daily and twenty one days after innoculation, animals were transfered to constant darkness for 24h. Tumour samples were collected at the implantation site at circadian time (CT)4 and CT16.
Publication Title
Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples