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Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to detail the global programme of gene expression after 4 months of TFEB overexpression in the brain.
Publication Title
Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Sex, Age, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs, and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Gp130 receptor engagement on neoplastic cells provides a link by which an inflammatory microenvironment facilitates tumour promotion. Although hyperactivation of the gp130-dependent Stat3 signalling node is commonly observed in solid tumours, Stat3 remains a challenging therapeutic target. To mimic excessive Stat3 signalling, we molecularly validate the gp130FF mouse as a preclinical model for inflammation-associated intestinal-type gastric cancer (IGC), with aberrant mammalian target of rapamycin (mTOR) pathway activity as shared feature. Accordingly, administration of the mTorc1 inhibitor RAD001 reversibly reduced IGC burden in gp130FF mice and suppressed colitis-associated cancer in wild-type mice. Since the therapeutic effect of RAD001 occurs independently of Stat3 hyperactivation, which is also dispensable for gp130-dependent engagement of the PI3K/Akt/mTorc1 pathway, we conclude that mTorc1 signalling limits tumour promoting Stat3 activity
Publication Title
mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Methods for identifying protein-protein interactions have mostly been limited to tagged exogenous expression approaches. We now establish a rapid, robust and comprehensive method for finding interacting proteins using endogenous proteins from limited cell numbers. We apply this approach called Rapid IP-Mass Spectrometry of Endogenous proteins (RIME) to identify ER, FoxA1 and E2F4 interacting proteins in breast cancer cells. From small numbers of starting cells, we find a comprehensive collection of known ER, FoxA1 and E2F4 targets, plus a number of novel unexpected interactors. One of the most ER (and FoxA1) associated interactors is GREB1, an estrogen induced gene with almost no known function. We apply RIME, in parallel with ER ChIP-seq, to identify ER protein interactors and ER binding events from solid tumor xenografts, resulting in the validation of the ER-GREB1 interactions. Furthermore, we establish a method for identifying endogenous interacting proteins from solid primary breast cancer samples, whih we apply to validate ER interactions with GREB1 and additional co-factors. Mechanistically, we show that GREB1 is recruited with ER to the chromatin where it functions as an essential estrogen-mediated regulatory factor required for effective ER transcriptional activity. Our novel approach enables, for the first time, the ability for discovery and validation of protein-protein interactions in whole tissue and solid tumors, revealing significant insight into ER regulatory factors.
Publication Title
Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina HiSeq 2500
Description
RNA-Seq data from intestinal tumors of ApcMin/+/Macrod2-/-,ApcMin/+/Macrod2-/+ and ApcMin/+/Macrod2+/+ mice (6 tumors per group) Overall design: Examine mRNA expression level changes between tumors by Macrod2 genotype
Publication Title
<i>MACROD2</i> Haploinsufficiency Impairs Catalytic Activity of PARP1 and Promotes Chromosome Instability and Growth of Intestinal Tumors.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Numerous studies have described the altered expression and the causal role of miRNAs in human cancer. However, to date efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here, we find that Nucleolin (NCL), a major nucleolar protein, post-transcriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, causally involved in breast cancer initiation, progression and drug-resistance. We also show that NCL is commonly overexpressed in human breast tumors, and its expression correlates with that of NCL-dependent miRNAs. Finally, this study indicates that NCL-binding guanosine-rich aptamers affect the levels of NCL-dependent miRNAs and their target genes, reducing breast cancer cell aggressiveness, both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.
Publication Title
In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance.
Publication Title
FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expansion of multipotent stem cells from the adult human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
GSE41467- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
Tissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Publication Title
Expansion of multipotent stem cells from the adult human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples