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SRP173650
Homo sapiens
28 Downloadable Samples
Illumina HiSeq 2500
Description
Pluripotent stem cells can switch their unique metabolic requirements to facilitate cellular changes but it is not clear if adult stem cells utilize metabolism in a similar manner. Here we studied the metabolism of a human adult stem cell: dental pulp stem cells (DPSCs). The dental pulp from third molars of a diverse patient group was surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteogenic and adipogenic lineages. Through RNA seq analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-ß) pathway and the proteins associated with muscle contraction are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs. This metabolic signature can be used to predict the onset of replicative senescence phenotypes. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging. Overall design: We did RNA-seq of dental pulp stem cells (DPSC) using our own approach (ID# 29, 43, 44, 45), as well as commercial DPSC and mesenchymal stem cells (MCS) from Lonza.
Publication Title
Metabolism as an early predictor of DPSCs aging.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Description
The polycomb repressive complex 2 (PRC2) histone methyl-transferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with sub-nanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESC) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development. Overall design: 1 biological sample were isolated from naïve hESC cell line Elf1 and Elf1 expressing EED binder 22.2. RNA-seq and ChIP-seq (H3K27me3) was performed for each sample.
Publication Title
First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 34 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The goal of this study was to identify the transcriptional mechanisms involved in the activation of the immune system by QS-21, a triterpene glycoside purified from the bark of Quillaja saponaria which has adjuvant activity in vivo. Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the Malaria and Zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T cell priming by QS-21 as revealed by the decrease in antigen-specific T cell response in Batf3/ mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans
Publication Title
Central Role of CD169<sup>+</sup> Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We established gene expression profiles of diagnostic bone marrow samples of monozygotic twins with acute lymphoblastic leukemia. We established technical duplicates for each twin.
Publication Title
Prenatal origin of separate evolution of leukemia in identical twins.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Sus scrofa
- 90 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced liver mRNA from 23 individual pigs (5 prefed and 18 fasted) taken at 4 separate time points to evaluate the change in gene expression over the course of hemorrhagic shock and resuscitation in response to a carbohydrate prefed state. Overall design: Examination of mRNA levels in liver biopsies from pigs at 4 timepoints throughout hemorrhagic shock and resuscitation
Publication Title
Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Early invasive growth and metastasis are features of pancreatic cancer that rely on resistance to anoikis, an apoptosis program activated upon loss of adequate matrix anchorage. Re-expression of the tumor suppressor p16 reversed anoikis resistance of pancreatic cancer cells. This conversion to an anoikis-susceptible phenotype was found to be associated with a striking loss of GNE mRNA expression, prompting us to address the role of GNE in pancreatic cancer in more detail. GNE catalyzes a rate-limiting key step of the sialic acid biosynthesis and may have additional functions in the nucleus.
Publication Title
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Early invasive growth and metastasis are features of pancreatic cancer that rely on resistance to anoikis, an apoptosis program activated upon loss of adequate matrix anchorage. Re-expression of the tumor suppressor p16 reversed anoikis resistance of pancreatic cancer cells. This conversion to an anoikis-susceptible phenotype was found to be associated with a striking loss of GNE mRNA expression, prompting us to address the role of GNE in pancreatic cancer in more detail. GNE catalyzes a rate-limiting key step of the sialic acid biosynthesis and may have additional functions in the nucleus.
Publication Title
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 88 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The biology underlying nodal metastasis is poorly understood. Transcriptome profiling has helped to characterize both primary tumors seeding nodal metastasis and the metastasis themselves. The interpretation of these data, however, is not without ambiguities. Here we profiled the transcriptomes of 17 papillary thyroid cancer (PTC) nodal metastases, associated primary tumors and primary tumors from N0 patients. We also included patient-matched normal thyroid and lymph node samples as controls to address some limits of previous studies. We found that the transcriptomes of patient-matched primary tumors and metastases were more similar than of unrelated metastases/primary pairs, a result also reported in other organ systems, and that part of this similarity reflected patient background. We found that the comparison of patient-matched primary tumors and metastases was heavily confounded by the presence of lymphoid tissues in the metastasis samples. An original data adjustment procedure was developed to circumvent this problem. It revealed a differential expression of stroma-related gene expression signatures also regulated in other organ systems. The comparison of N0 vs. N+ primary tumors uncovered a signal irreproducible across independent PTC datasets. This signal was also detectable when comparing the normal thyroid tissues adjacent to N0 and N+ tumors, suggesting a cohort specific bias also likely to be present in previous studies with similar statistical power. Classification of N0 vs. N+ yielded an accuracy of 63%, but additional statistical controls not presented in previous studies, revealed that this is likely to occur by chance alone. To address this issue, we used large datasets from The Cancer Genome Atlas and showed that N0 vs. N+ classification rates could not be reached randomly for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers.
Publication Title
Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Kaposis sarcoma (KS) is the most frequently occurring malignant tumor in patients infected with the human immunodeficiency virus. Recent studies have revealed that infection of vascular endothelial cells with Kaposi's sarcoma-associated herpes virus in vitro results in a lymphatic re-programming of these cells, with potent induction of the lymphatic marker genes podoplanin and VEGFR-3 which is mediated by upregulation of the transcription factor Prox1. However, the potential effects of Prox1 expression on the biology of KS and, in particular, on the aggressive and invasive behavior of KS tumors in vivo have remained unknown. We stably expressed Prox1 cDNA in the two mouse hemangioendothelioma cell lines EOMA and Py-4-1, well-established murine models for kaposiform hemangioendothelioma. Surprisingly, we found that expression of Prox1 was sufficient to induce a more aggressive behavior of tumors growing in syngenic mice, leading to enhanced local invasion into the muscular layer and to cellular anaplasia. This enhanced malignant phenotype was associated with upregulation of several genes involved in proteolysis, cytoskeletal reorganisation and migration. Together, these results indicate that Prox1 plays an important, previously unanticipated role in mediating the aggressive behavior of vascular neoplasms such as Kaposi's sarcoma.
Publication Title
Prox-1 promotes invasion of kaposiform hemangioendotheliomas.
Sample Metadata Fields
No sample metadata fields
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