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GSE50603
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We found that the non-essential amino acid L-Proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells (ESCs) into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic stem cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the transcriptome
Publication Title
L-Proline induces a mesenchymal-like invasive program in embryonic stem cells by remodeling H3K9 and H3K36 methylation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required. Overall design: Examination of mRNA levels in Zfp57-/- mouse ESCs compared to the wild-type.
Publication Title
ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500, NextSeq 500
Description
Samples 1-4 report RNA-seq transcriptome profiling of the L-Proline- (L-Pro) and bFgf/ActivinA- (F/A) derived mCherry+/eGFP+ (yellow) ESC population, using the Illumina HiSeq platform. Whole-genome expression revealed that more than 1000 genes were significantly deregulated in L-Pro- and F/A-induced cells compared to control (mCherry+/eGFP- red cells) and the two population shared up to 75% of deregulated genes with the same deregulation trend. Specifically, the pluripotency-associated genes were downregulated either at similar level (Nanog, Klf2, Klf4 and Gbx2) or at lower levels (up to 10 times) (Dppa 2, 3, 4, 5a, Rex1, Esrrb) in F/A- compared to L-Pro-treated cells. Interestingly, mesendodermal-related genes (e.g. Brachyury, Cer1, Dkk1, Eomes, Foxa2, and Sox17) were induced in both conditions but at significant higher levels in F/A- compared to L-Pro-treated cells. The transcriptome analysis of mCherry+/eGFP+ (yellow) cells supported the idea that L-Pro mimics F/A in inducing a naïve to primed transition, and suggested that it exerted a milder (weaker) effect. Samples 5-14 report RNA-seq transcriptome profiling of the mir-290_mCherry/mir-302_eGFP dual reporter ESCs (DRESCs) bulk culture, grown in FBS/LIF ± VitaminC (VitC) and L-Proline (L-Pro) and compared them to the standard naive/2i and primed/bFgf/ActivinA-EpiSCs (F/A), using the Illumina HiSeq platform. Whole-genome expression identified around 7900 deregulated genes in the different conditions, (fold change=2 and pvalue<0.05). Principal component analysis (PCA) placed VitC between 2i and untreated control, and L-Pro between control and F/A. Accordingly, a set of pluripotency-associated genes was expressed at higher level in 2i and VitC conditions, while downregulated in L-Pro and F/A, compared to control. Conversely, priming markers were downregulated in 2i and VitC and upregulated in L-Pro and F/A compared to control The transcriptome analysis supported that VitC- and L-Pro captured alternative pluripotency states that can be likely placed between naïve/2i and primed/F/A states. Overall design: RNA-seq profiling of ESCs grown in FBS/LIF ± VitC, 2i, L-Pro or F/A, using the Illumina HiSeq platform
Publication Title
Vitamin C and l-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum.
Sample Metadata Fields
Cell line, 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