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SRP109188
Homo sapiens
9 Downloadable Samples
Illumina HiSeq 4000
Description
Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation in the absence of genetic mutations is not clear. To investigate this question, we use a CRISPR/dCas9 based epigenetic editing tool, where an inactive form of Cas9 is fused to DNMT3A and its regulator DNMT3L. Using this system, we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary myoepithelial cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct and results in sustained repression of CDKN2A and RASSF1 transcripts which prevents cells from entering senescence. The phenotype is associated with retuned expression of a subset of genes to levels in early passage cells; however, the outgrowing myoepithelial cells are not immortal but proliferate for 18-20 population doublings before cell cycle arrest. Finally, we show that the key driver of this phenotype is repression of CDKN2A transcript p16, but prolonged proliferation is enhanced by combined hypermethylation and repression of both CDKN2A transcripts p16 and p14. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, a potential first step in the disease process. Overall design: RNA-seq experiment with n=3 biological replicates of primary myoepithelial transfection with 26x gRNAs targeting DNA methylation as described.
Publication Title
Hit-and-run epigenetic editing prevents senescence entry in primary breast cells from healthy donors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. A significant proportion of Pbx1-dependent genes are associated with the Tgf-b pathway, which serves a major role in maintaining HSC quiescence. Pbx1-deficient LT-HSCs are unable to up-regulate the cyclin dependent kinase inhibitor p57 in response to Tgf-b, providing a mechanism through which Pbx1 maintenance of stem cell self-renewal is achieved.
Publication Title
Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors.
Publication Title
Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Chronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction.
Publication Title
Behavioral and transcriptional patterns of protracted opioid self-administration in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner. However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs. In addition to a profound defect in hematopoietic stem cell (HSC) self-renewal, conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors, including common myeloid progenitors (CMPs) and, to a lesser extent, granulocyte-monocyte progenitors (GMPs).
Publication Title
Pbx1 restrains myeloid maturation while preserving lymphoid potential in hematopoietic progenitors.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study was performed to check that ESR1 and BMI1 are biologically active after lentiviral transduction of primary human mammary epithelial cells (HMECs) with lentiviral vectors expressing ESR1 and BMI1 from the human PGK promoter. ESR1 targets like PGR, PRLR and GREB1, but not TFF1 and XBP1, were induced by estradiol in the ESR1-expressing cells. BMI1 targets like BMI1, NEFL and CCND2 were repressed in the BMI1-expressing cells. BMI1 suppressed genes associated with squamous and neural differentiation in the ESR1 plus BMI1-expressing cells.
Publication Title
An oestrogen-dependent model of breast cancer created by transformation of normal human mammary epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human leukemia cell line RS4.11 was treated with GSK-3 inhibitor SB216763 for 20 hours. Gene expression profiling was performed to analyze genes affected by GSK-3 inhibition.
Publication Title
GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
The most immature progenitors in the murine thymus are early T lineage progenitors (ETP). These cells are the precursors of more mature thymocytes that ultimately leave the thymus and colonize peripheral lymphoid tissues. As part of our efforts to define age-related changes in ETP, we harvested them from mice of different ages and performed whole transcriptome profiling. This analysis revealed major differences in patterns of gene expression between young and old ETP, and we were particularly struck by the significantly reduced expression of the gene encoding high mobility group A 2 protein (Hmga2). Overall design: The experiment compares gene expression in young adult (4-6 week old) and old (72 week old) mouse Early T Lineage Progenitors (ETP)
Publication Title
The expansion of thymopoiesis in neonatal mice is dependent on expression of high mobility group a 2 protein (Hmga2).
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Head and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping
Publication Title
Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer.
Sample Metadata Fields
No sample metadata fields
View Samples