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Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Methods of reprogramming somatic cells to an induced pluripotent state (iPSC) have enabled the direct modeling of human disease and ultimately promise to revolutionize regenerative medicine. iPSCs offer an invaluable source of patient-specific pluripotent stem cells for disease modeling, drug screening, toxicology tests and importantly for regenerative medicine, and already have been employed to unmask novel insights into human diseases. While iPSCs can be consistently generated through overexpression of the four Yamanaka Factors OCT4, SOX2, KLF4 and c-MYC (OSKM), reprogrammed cells present worrisome differences with embryonic stem cells in transcriptional and epigenetic profiles, as well as developmental potential and difficulties in cell culturing. A thorough mechanistic understanding of the reprogramming process is critical to overcoming these barriers to the clinical use of iPSC. We have recently published a novel factor combination based on molecules specifically enriched in the metaphase II human oocyte. We have shown that just the overexpression of histone-remodeling chaperone ASF1A and OCT4 in hADFs previously exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells (AO9-iPSCs). Our study contributes to the understanding of the molecular pathways governing somatic cell reprogramming. Here we want to go deeper in the reprogramming mechanisms by understanding the importance of somatic cell origin, and analyzing (and establishing comparison with) the transcriptional and epigenetic characteristics of AO9-iPSCs. As the intrinsic histone chaperone activity of ASF1A and our data indicate, these cells could be closer to the embryonic pluripotent state, with less epigenetic memory, better culture properties and differentiation potential.
Publication Title
Analysis of Menstrual Blood Stromal Cells Reveals SOX15 Triggers Oocyte-Based Human Cell Reprogramming.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify gene(s) that are modified in their relative expression levels in the Potocki-Lupski Syndrome mouse model and map to the rearranged region, i.e. possible candidate genes at the source of the PTLS-like phenotypes shown by the PTLS mouse, we comp
Publication Title
Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The statins are a family of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme, which converts acetyl-CoA into mevalonic acid. Since HMG-CoA reductase catalyzes the rate-limiting step in the mevalonate pathway of cholesterol biosynthesis, it was thought that the major clinical benefit of statins was to reduce cholesterol levels in the bloodstream; statins are thus in wide clinical use for the prevention and treatment of cardiovascular disease. Nonetheless, mevalonate is also the precursor of isoprenoid compounds, which are substrates for the post-translational modification of many proteins involved in cell signaling. The blockade of isoprenoid synthesis might explain the pleiotropic effects described for statins in extrahepatic tissues, including inhibition of pathogen infection and anti-inflammatory and immunomodulatory activities.
Publication Title
A lovastatin-elicited genetic program inhibits M2 macrophage polarization and enhances T cell infiltration into spontaneous mouse mammary tumors.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Gallus gallus
- 8 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Neural crest cells are a transient embryonic population, hence are neither present after bith and nor are they readily accesible for analysis. Therefore, little is known about the genetic networks that regulate NC especification, delamitation and migration from the dorsal neural tube to their final destination along the embryo.
Publication Title
Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
LRRK2 mutations are the most common genetic cause of Parkinsons disease (PD). We performed a whole-genome RNA profiling of locus coeruleus post-mortem tissue from idiopathic PD (IPD) and LRRK2-associated PD patients. The differentially expressed genes found in IPD and LRRK2-associated PD were involved in the gene ontology terms of synaptic transmission and neuron projection. In addition, in the IPD group we found associated genes belonging to the immune system. Pathway analysis of the differentially expressed genes in IPD was related with neuroactive-ligand receptor interaction and with immune system pathways. Specifically, the analysis highlighted differential expression of genes located in the chromosome 6p21.3 belonging to the class II HLA. Our findings support the hypothesis of a potential role of neuroinflammation and the involvement of the HLA genetic area in IPD pathogenesis. Future studies are necessary to shed light on the relation of immune system related pathways in the etiopathogenesis of PD.
Publication Title
Brain transcriptomic profiling in idiopathic and LRRK2-associated Parkinson's disease.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Our lab established the M0505 cell line from the ovarian surface epithelium (OSE) of FVB/N mice in May 2005 in order to study OSE biology. This cell line spontaneously transformed into the spontaneously transformed OSE (STOSE) cell line in mid 2012.
Publication Title
A new spontaneously transformed syngeneic model of high-grade serous ovarian cancer with a tumor-initiating cell population.
Sample Metadata Fields
Specimen part
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E-MTAB-912- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
Publication Title
Induction of autophagy by spermidine promotes longevity.
Sample Metadata Fields
Age, Compound, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We have found the existence of a Bmi1+ population in the adult heart contributing to the organ low-rate turnover and repair with the generation of new cardiomyocytes. We show that the Bmi1+ population is a sub-population of the cardiac Sca-1+ progenitor cells. We have analyzed the gene profile by deep-sequencing (RNA-Seq) of Bmi1+ and Sca-1+Bmi1- cells in homeostatic heart condition. On the other hand, we have compared gene profile by deep-sequencing (RNA-Seq) of Bmi1+ cells in homeostatic condition versus Bmi1+ cells 5 days after myocardial infarction (MI). Analysis of RNA-Seq data revealed a differential expression signature between both subsets of cardiac stem/progenitors cells in homeostatic condition and also differences between Bmi1+ cells after AMI versus homeostatic condition. Overall design: Examination of gene profile of 2 different cardiac stem /progenitors subsets (Bmi1+ and Sca-1+Bmi1-) co-existing inthe adult heart under steady state. Examination of gene profile of Bmi1+ cardiac stem cells in homeostatic condition versus MI
Publication Title
Age-related oxidative stress confines damage-responsive Bmi1<sup>+</sup> cells to perivascular regions in the murine adult heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
LRRK2 mutations are the most common genetic cause of Parkinsons disease (PD). We performed a whole-genome RNA profiling of putamen tissue from idiopathic PD (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST Array. The differentially expressed genes found in IPD revealed an alteration of biological pathways related to long term potentiation (LTP), GABA receptor signalling, and calcium signalling pathways, among others. These pathways are mainly related with cell signalling cascades and synaptic plasticity processes. They were also altered in the asymptomatic LRRK2 mutation carrier but not in the LRRK2-associated PD group. The expression changes seen in IPD might be attributed to an adaptive consequence of a dysfunction in the dopamine transmission. The lack of these altered molecular pathways in LRRK2-associated PD patients suggests that these cases could show a different molecular response to dopamine transmission impairment.
Publication Title
Microarray expression analysis in idiopathic and LRRK2-associated Parkinson's disease.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
The tumor suppressor TP53 is mutated in the majority of human cancers, including over 70% of pancreatic ductal adenocarcinoma (PDAC). Wild-type p53 accumulates in response to cellular stress and regulates the expression of genes that alter cell fate and constrain tumorigenesis. p53 also modulates several cellular metabolic pathways, though it remains unclear whether particular p53-regulated metabolites contribute to tumor suppression or whether metabolic alterations driven by p53 mutation sustain cancer progression. Here, we show that restoring endogenous p53 function in cancer cells derived from a murine PDAC model driven by oncogenic Kras and a regulatable p53 short hairpin RNA (shRNA) rewires glucose and glutamine metabolism leading to the accumulation of a-ketoglutarate (aKG), an obligate substrate for several chromatin modifying enzymes. p53 induces transcriptional programs characteristic of premalignant differentiation, an effect that can be partially recapitulated by addition of cell permeable aKG. Similarly, enforcing aKG accumulation in p53-deficient PDAC cells though the inhibition of oxoglutarate (aKG) dehydrogenase (Ogdh), the enzyme that consumes aKG in the tricarboxylic acid cycle, reduces tumor-initiating capacity and promotes tumor cell differentiation. Decreases in 5-hydroxymethylcytosine (5hmC), an aKG-dependent chromatin modification, are associated with the appearance of p53 mutations in the transition from premalignant to de-differentiated malignant lesions, whereas increases in 5hmC accompany tumor cell differentiation triggered by either p53 restoration or Ogdh depletion. Together these data nominate aKG as an effector of p53-mediated tumor suppression whose accumulation in p53-deficient tumors can drive tumor cell differentiation and antagonize malignant progression. Overall design: 6 samples were analyzed in duplicates of 3 conditions. 1. Control, KPsh cells grown on dox, treated with vehicle DMSO for 72 hours. 2. KPsh cells grown on dox, treated with 4mM cell permeable dimethyl-alpha ketoglutarate for 72 hours. 3. KPsh cells grown off dox for 8 days, treated with DMSO vehicle for 72 hours.
Publication Title
α-Ketoglutarate links p53 to cell fate during tumour suppression.
Sample Metadata Fields
Cell line, Treatment, Subject
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