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Homo sapiens
12 Downloadable Samples
Illumina HiSeq 2500
Description
The p53 protein is the most frequently inactivated tumor suppressor in human cancer. While p53 mutations are found in 50% of all cancers, the p53 pathway can also be suppressed by its interaction with endogenous inhibitors HDMX and HDM2, which are frequently overexpressed in patients with acute myeloid leukemia and other cancers. Thus, pharmacological disruption of both these interactions is an attractive strategy to restore p53-dependent tumor suppressor activity in AML with wild type P53. Strategies targeting HDM2 have recently generated promising results; however, cancer cells are still left vulnerable to p53 inhibition by HDMX, particularly in cancers such as leukemia that overexpress HDMX. In this study, we demonstrate that dual HDMX/HDM2 inhibition using a stapled alpha-helical peptide (ALRN-6924), which has recently entered clinical testing, leads to striking anti-leukemic effects. ALRN-6924 robustly activates p53-dependent transcription at the single cell and single molecule level, and exhibits biochemical and molecular biological on-target activity in leukemia cells in vitro and in a patient who received ALRN-6924 treatment. Dual HDMX/HDM2 inhibition by ALRN-6924 inhibits cellular proliferation by inducing cell cycle arrest and apoptosis in cell lines and primary AML patients' cells, including in leukemic stem cell-enriched populations, and disrupts functional clonogenic and serial replating capacity. Furthermore, ALRN-6924 leads to significantly improved survival in an AML xenograft model in vivo. At the molecular level, dual HDMX/HDM2 inhibition leads to global transcriptional activation of p53-dependent pathways in leukemia cells. Our study provides insight into the effects of dual HDMX/HDM2 inhibition and proof-of-concept for ALRN-6924 as a novel therapeutic approach in AML and other cancers with high HDMX levels. Overall design: Total mRNA expression profiles of vehicle (1:10 DMSO) or 1 uM ALRN-6924 treated AML cells (6 hours) were generated by deep sequencing, in triplicates, using the Illumnia HiSeq 2500 instrument.
Publication Title
Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The immortalized human urothelial cell line, UROtsa, was transformed in six parallel cultures with continual passaging in1 M Cd+2 until the cells were able to attain the ability to form colonies in soft agar and subcutaneous tumors in nude mice. The gene expression profiles between cadmium-transformed and control samples were compared and the differentially expressed genes were identified.
Publication Title
Variation of keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells (UROtsa).
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction between MSCs and the innate immune comaprtment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1M) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1M and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens new perspectives for MSC-based cell therapy.
Publication Title
CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage.
Publication Title
CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 66 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
An 11-point time course study comparing V6.5 embryonic stem cells versus embryoid bodies. Time course 0 hours, 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 4 days, 7 days, 9 days, and 14 days.
Publication Title
Gene function in early mouse embryonic stem cell differentiation.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 66 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
An 11-point time course study comparing R1 embryonic stem cells versus embryoid bodies. Time course 0 hours, 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 4 days, 7 days, 9 days, and 14 days.
Publication Title
Gene function in early mouse embryonic stem cell differentiation.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 66 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
An 11-point time course study on differentiating embryoid bodies from a murine J1 embryonic stem cell line. The time course includes 0 hr, 6 hr, 12 hr, 18 hr, 24 hr, 36 hr, 48 hr, 4 days, 7 days, 9 days and 14 days.
Publication Title
Gene function in early mouse embryonic stem cell differentiation.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 58 Downloadable Samples
- NextSeq 500
Description
Data accompaning to van Gurp et al. Development 2019. single-cell sequencing of the developing mouse pancreas followed by Seurat analysis to discover genes important for alpha and beta cell differentiation. Overall design: Single-cells from mouse embryonic pancreas at E12.5, E13.5, E14.5, E15.5 and E18.5 were isolated and enriched for MIP-GFP and sorted into 384-well plates. Afterwards, SORT-seq was performed and single-cell transcriptomics profiles were obtained.
Publication Title
A transcriptomic roadmap to α- and β-cell differentiation in the embryonic pancreas.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. The purpose of this experiment was to characterize the transcriptomic changes associated with macrophage aging.
Publication Title
Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples
GSE2866- Mus musculus
- 18 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Succinate semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder effecting approximately 350 people around the world. Patients suffering from SSADH deficiency experience language acquisition failure, memory deficiencies, autism, increased aggressive behaviors, and seizures. There is a chemical buildup of both gamma-aminobutyric acid (GABA) and gamma-hydroxybutyric acid (GHB) in the neurological system of these patients. The Aldh5a1-/- knock out mouse model of SSADH deficiency shows the same chemical imbalances as the human disease, with additional fatal tonic-clonic seizures at three weeks of age. The elucidation of seizure causing pathways will facilitate treatment of seizure phenotypes in diseases with related epilepsy.
Publication Title
Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency.
Sample Metadata Fields
No sample metadata fields
View Samples