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Homo sapiens
16 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Defining the aging-cancer relationship is a challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate many features of aging. However, their short lifespan and cell-intrinsic and -extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. To circumvent these limitations we have generated Zmpste24 mosaic mice. Interestingly, these mice develop normally - revealing cell-extrinsic mechanisms are preeminent in progeria- and display decreased incidence of infiltrating oral carcinomas. Moreover, ZMPSTE24 knock-down reduces human cancer cell invasiveness. Our results disclose the ZMPSTE24-prelamin A system as an example of antagonistic pleiotropy on cancer and aging, support the potential of cell-based and systemic therapies for progeria, and highlight ZMPSTE24 as a new anticancer target.
Publication Title
Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion.
Sample Metadata Fields
Cell line
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SRP059989- Homo sapiens
- 10 Downloadable Samples
IlluminaHiSeq2000
Description
By means of 3' end sequencing we provide a genome-wide, high-resolution polyadenylation map of the human heart. By sequencing 5 control en 5 dilated cardiomyopathy (DCM) myocardial specimens we investigate the difference in alternative polyadenylation (APA) in healthy and diseased hearts.
Publication Title
Genome-Wide Polyadenylation Maps Reveal Dynamic mRNA 3'-End Formation in the Failing Human Heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
One of the challenges of current research in prostate cancer is to improve the differential non-invasive diagnosis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer patients exhibit genuine and differential physical and biological properties. Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in prostate cancer.
Publication Title
Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understand the aging process.
Publication Title
Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. While it is well established that many of the age-induced changes are intrinsic to HSCs, less is known about the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and following the transplantation of 're-differentiated' HSCs into new hosts; the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results therefore favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging rather than being driven by an increased DNA mutation burden.
Publication Title
An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Genome wide RNA-seq from pGM and HSCs in response to expression of the MLL-ENL fusion gene Overall design: Examination of mRNA abundance in two cell types with or without induction of the MLL-ENL fusion gene (following 48h of culture)
Publication Title
Hematopoietic stem cells are intrinsically protected against MLL-ENL-mediated transformation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Glyphosate-based herbicides are the major pesticides used worldwide. There is an intense debate on the estrogenic effects of their ingredients. We have compared the estrogenic effects of glyphosate (the active principle), polyethoxylated tallowamine (a co-formulant), and a commercial formulations containing different co-formulants to those of estradiol and bisphenol A in the MCF-7 human breast cancer cell line. The gene expression profiles were determined using the Affymetrix Human Transcriptome 2.0 Array.
Publication Title
Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We developed a novel culture system to obtain multilineage undifferentiated stem/progenitor cells from normal human thyroid tissues. This seems to be achieved by direct reprogramming of thyroid follicular cells. The objective of the study was to reveal gene expression profile of the obtained cells compared to primary thyrocytes. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin and cytokeratin-18, were cultured in a serum-free medium called SAGM containing insulin and EGF. Although the vast majority of cells died, a small proportion (~0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined, suggesting that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions.
Publication Title
Dedifferentiation of human primary thyrocytes into multilineage progenitor cells without gene introduction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Considering the numerous complex and different pathological mechanisms involved in Alzheimers disease (AD) progression, treatments targeting a single cause may lead to limited benefits. The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.
Publication Title
Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion between pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem and progenitor cells (HSPCs), and mature hematopoietic cells. Quantification of chromatin composition by high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSPCs, with a further reduction in euchromatin as HSPCs transition into mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9a resulted in delayed hematopoietic stem cell (HSC) differentiation. Our results demonstrate significant global rearrangements of chromatin structure during embryonic and adult stem cell differentiation, and that heterochromatin formation by H3K9 methylation is an important regulator of HSC differentiation. Overall design: Examination of gene expression profile of in vitro cultured mouse HSC with the G9a inhibitor UNC0638
Publication Title
Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
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