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GSE49897
Homo sapiens
4 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Hematopoietic stem cells (HSCs), which reside in bone marrow niches, are exposed to low levels of oxygen and follow an oxygen gradient throughout their differentiation. Hypoxia-inducible factors (HIFs) are the main factors regulating the cell response to oxygen variation. Recent studies using conditional knockout mouse models have unveiled a major role of HIF-1a in the maintenance of murine HSCs, however the role of HIF-2a is still unclear. Here, we show that knockdown of HIF-2a and to a much lower extent, HIF-1a impedes the long-term repopulating ability of human CD34+ umbilical cord blood derived cells. The defects observed in hematopoietic stem and progenitor cell (HSPC) function after HIF-2a knockdown was due to an increase in the production of reactive oxygen species (ROS), which increases the endoplasmic reticulum (ER) stress in HSPCs and triggers apoptosis by the activation of the unfolded-protein-response (UPR) pathway. Importantly, HIF-2a deregulation also resulted in a significant decrease of engraftment of human acute myeloid leukemia (AML) cells. Overall, our data demonstrates a key role of HIF-2a in the maintenance of human HSPCs and in the survival of primary AML cells.
Publication Title
HIF-2α protects human hematopoietic stem/progenitors and acute myeloid leukemic cells from apoptosis induced by endoplasmic reticulum stress.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 7 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 7 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The Scc2/Scc4 complex binds to broad nucleosome-free regions in the promoters of highly expressed genes. The cohesin loader is recruited to these sites by the RSC chromatin remodeling complex
Publication Title
The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Cohesin acetylation by Eco1 during DNA replication establishes sister chromatid cohesion. We show that acetylation makes cohesin resistant to Wapl activity from S-phase until mitosis. Wapl turns out to be a key regulator of cohesin dynamics on chromosomes by controling cohesin maintenance following its establishment in S-phase and its role in chromosome condensation.
Publication Title
Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone acetylation and other modifications of the chromatin are important regulators of gene expression and, consequently, may contribute to drug-induced behaviors and neuroplasticity. Previous studies have shown that a reduction on histone deacetylase (HDAC) activity results on the enhancement of some psychostimulant-induced behaviors. In the present study, we extend those seminal findings by showing that the administration of the HDAC inhibitor sodium butyrate enhances morphine-induced locomotor sensitization and conditioned place preference. In contrast, this compound has no effects on the development of morphine tolerance and dependence. Similar effects were observed for cocaine and ethanol-induced behaviors. These behavioral changes were accompanied by a selective boosting of a component of the transcriptional program activated by chronic morphine administration that included circadian clock genes and other genes relevant in addictive behavior. Our results support an specific role for histone acetylation and the epigenetic modulation of transcription at a reduced number of biologically relevant loci on non-homeostatic, long lasting, drug-induced behavioral plasticity. To further investigate the molecular bases of sodium butyrate action on long-lasting behavioral responses to morphine, we screened for potential substrates of their interaction by performing a genome-wide comparison of the striatal transcriptome after chronic administration of morphine in the absence or presence of sodium butyrate.
Publication Title
Selective boosting of transcriptional and behavioral responses to drugs of abuse by histone deacetylase inhibition.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Methods of reprogramming somatic cells to an induced pluripotent state (iPSC) have enabled the direct modeling of human disease and ultimately promise to revolutionize regenerative medicine. iPSCs offer an invaluable source of patient-specific pluripotent stem cells for disease modeling, drug screening, toxicology tests and importantly for regenerative medicine, and already have been employed to unmask novel insights into human diseases. While iPSCs can be consistently generated through overexpression of the four Yamanaka Factors OCT4, SOX2, KLF4 and c-MYC (OSKM), reprogrammed cells present worrisome differences with embryonic stem cells in transcriptional and epigenetic profiles, as well as developmental potential and difficulties in cell culturing. A thorough mechanistic understanding of the reprogramming process is critical to overcoming these barriers to the clinical use of iPSC. We have recently published a novel factor combination based on molecules specifically enriched in the metaphase II human oocyte. We have shown that just the overexpression of histone-remodeling chaperone ASF1A and OCT4 in hADFs previously exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells (AO9-iPSCs). Our study contributes to the understanding of the molecular pathways governing somatic cell reprogramming. Here we want to go deeper in the reprogramming mechanisms by understanding the importance of somatic cell origin, and analyzing (and establishing comparison with) the transcriptional and epigenetic characteristics of AO9-iPSCs. As the intrinsic histone chaperone activity of ASF1A and our data indicate, these cells could be closer to the embryonic pluripotent state, with less epigenetic memory, better culture properties and differentiation potential.
Publication Title
Analysis of Menstrual Blood Stromal Cells Reveals SOX15 Triggers Oocyte-Based Human Cell Reprogramming.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptional dysregulation is an important early feature of polyglutamine diseases. One of its proposed causes is defective neuronal histone acetylation, but important aspects of this hypothesis, such as the precise genomic topography of acetylation deficits
Publication Title
Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
STAT2 is an essential transcription factor in type I interferon (IFN) signaling. STAT2 mediates the antigrowth and apoptotic effects of IFN as demonstrated in cell lines thus leading to the hypothesis that STAT2 has tumor suppressor function.
Publication Title
Host STAT2/type I interferon axis controls tumor growth.
Sample Metadata Fields
Specimen part
View Samples