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GSE64957
Homo sapiens
54 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Learn about the transcriptome profiling of zona glomerulosa (ZG), zona fasciculata (ZF) and aldosterone-producing adenomas (APA) in human adrenals
Publication Title
DACH1, a zona glomerulosa selective gene in the human adrenal, activates transforming growth factor-β signaling and suppresses aldosterone secretion.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof-of-principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC dependent cancers as well. Overall design: RNA sequencing of MOLP-8 cells transduced with lentiCRISPRv2 scrambled control or containing a sgRNA against LIN28B. Both control and LIN28B KO cells were sequenced in triplicate.
Publication Title
The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 41 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Heirarchical development of B-cells involves the induction and supression of large sets of genes that provide the basis for differentiation and, ultimately, antibody production.
Publication Title
Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Medulloblastoma is the most frequent malignant pediatric brain tumor. Considerable efforts are dedicated to identify markers that help to refine treatment strategies. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favorable patient outcome. We report a series of 72 pediatric medulloblastomas evaluated for beta-catenin immunostaining, CTNNB1 mutations, and studied by comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumor cells) in 6 cases and focal nuclear staining (<10% of cells) in 3 cases. The other cases exhibited either a signal strictly limited to the cytoplasm (58 cases) or were negative (5 cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented a strong activation of the Wnt/beta-catenin pathway. Remarkably, 5 out of these 6 tumors showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumors with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2) from diagnosis. All three patients with a focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumors represent a distinct molecular subgroup of medulloblastomas with favorable outcome, indicating that therapy de-escalation should be considered. Yet, international consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved.
Publication Title
Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Progestins have long been used clinically for the treatment of endometrial cancers, however, the response rates to progestin therapy vary and the molecular mechanisms behind progestin insensitivity are poorly understood. We hypothesized that in PTEN mutated endometrial cancers, hyperactive Akt signaling downregulates Progesterone Receptor B (PRB) transcriptional activity, leading to overall impaired progestin responses. We report that knockdown of Akt is sufficient to upregulate a subset of PRB target genes.
Publication Title
Akt regulates progesterone receptor B-dependent transcription and angiogenesis in endometrial cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124a directly targets PTBP1/PTB/hnRNPI mRNA, which encodes a global repressor of alternative pre-mRNA splicing in non-neuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2/nPTB/brPTB, an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay. During neuronal differentiation, miR-124a reduces PTBP1 levels leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124a plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124a promotes NS development at least in part by regulating an intricate network of NS-specific alternative splicing.
Publication Title
The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 66 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Environmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes suggesting a general alteration in genome activity. Investigation of eleven different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had unique transgenerational transcriptomes. Common cellular pathways and processes were identified among the tissues. A bionetwork analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue specific gene expression and function. A large number of statistically significant over-represented clusters of differentially expressed genes were identified and termed Epigenetic Control Regions. Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome appear to in part coordinately regulate these tissue specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes.
Publication Title
Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
WT and Ikbke-/- EF cells were stimulated with recombinant interferon beta for 6 hours. Cells lacking IKKe kinase show a defect in a subset of interferon stimulated gene transcription
Publication Title
Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We use gene expression data to provide a three-faceted analysis on the links between molecular subclasses of glioblastima, epithelial-to mesenchymal transition (EMT) and CD133 cell surface protein. The contribution of this paper is three-folded: First, we used a newly identified signature for epithelial-to-mesenchymal transition in human mammary epithelial cells, and demonstrated that genes in this signature have significant overlap with genes differentially expressed in all known GBM subtypes. However, the overlap between the genes up-regulated in the mesenchymal subtype of GBM and in the EMT signature was more significant than other GBM subtypes. Second, we provided evidence that there is a negative correlation between the genetic signature of EMT and that of CD133 cell surface protein, a putative marker for neural stem cells. Third, we studied the correlation between GBM molecular subtypes and the genetic signature of CD133 cell surface protein. We demonstrated that the mesenchymal and neural subtypes of GBM have the strongest correlations with the CD133 genetic signature. While the mesenchymal subtype of GBM demonstrates similarity with the signatures of both EMT and CD133, it also demonstrates some differences with each of these signatures that is partly due to the fact that the signatures of EMT and CD133 are inversely related to each other. Taken together this data sheds light on role of the mesenchymal transition and neural stem cells, and their mutual interaction, in molecular subtypes of glioblastoma multiforme.
Publication Title
Investigating the link between molecular subtypes of glioblastoma, epithelial-mesenchymal transition, and CD133 cell surface protein.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We analyzed via microarray gene expression profiles in de-identified, clinically annotated samples from Ficoll-purified peripheral blood samples from 10 acute myeloid leukemia (AML) patients in remission and 10 healthy donors collected under IRB-approved protocols.
Publication Title
Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples