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GSE144638
Homo sapiens
14 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
Pediatric Acute Myeloid Leukemia (AML) is an aggressive and poor prognosis malignancy for which there are few effective targeted approaches, despite the numerous genetic alterations, including MLL gene rearrangements (MLL-r). The histone methyltransferase DOT1L is involved in supporting proliferation of MLL-r cells, for which a target inhibitor, Pinometostat, has been evaluated in a clinical trial recruiting pediatric MLL-r leukemic patients. However, modest clinical effects have been reported. Recent studies reported that additional leukemia subtypes lacking MLL-r are sensitive to DOT1L inhibition. Here we report that targeting DOT1L with Pinometostat sensitizes pediatric AML cells to further treatment with the multi-kinase inhibitor Sorafenib, irrespectively of MLL-r. DOT1L pharmacologic inhibition induces AML cell differentiation and modulated expression of genes with relevant roles in cancer development. Such modifications in transcriptional program impact on further treatments, inducing a strong sensitization to Sorafenib, with increased apoptosis and growth suppression of both AML cell lines and primary pediatric AML cells with diverse genotypes. We used microarrays to define differential regulation of gene expression in AML cell lines with or without MLL gene rearrangements following pharmacologic inhibition of DOT1L.
Publication Title
Inhibition of Methyltransferase DOT1L Sensitizes to Sorafenib Treatment AML Cells Irrespective of <i>MLL</i>-Rearrangements: A Novel Therapeutic Strategy for Pediatric AML.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 17 Downloadable Samples
Illumina HiSeq 2500
Description
We show that mesenchymal CSC-like cells express an embryonic stem cell signature that is mutant p53 dependent Overall design: Examination of three p53 mutant mesenchymal stem cells and ten derived CSC-like cell lines and 2 derived p53 mutant KO clones compared to control clones
Publication Title
A Mutant p53-Dependent Embryonic Stem Cell Gene Signature Is Associated with Augmented Tumorigenesis of Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Bos taurus
- 18 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Sexual dimorphism in mammals is mostly attributable to sex-related hormonal differences in fetal and adult tissues; however, this may not be the sole determinant. Though genetically-identical for autosomal chromosomes, male and female preimplantation embryos could display sex-specific transcriptional regulation which can only be attributted to the differences in sexual chromosome dosage.
Publication Title
Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The molecular mechanisms underlying the great differences in susceptibility to noise-induced hearing loss (NIHL) exhibited by both humans and laboratory animals are unknown. Using microarray technology, the present study demonstrates that the effects of noise overexposure on the expression of molecules likely to be important to the development of NIHL differ among inbred mice that have distinctive susceptibilities to NIHL including B6.CAST, 129X1/SvJ, and 129S1/SvImJ. The noise-exposure protocol produced, on average, a permanent loss of about 40 dB in sensitivity for auditory brainstem responses in susceptible B6.CAST mice, but no threshold elevations for the two resistant 129S1/SvImJ and 129X1/SvJ substrains. Measurements of noise-induced gene expression changes 6 h after the noise exposure revealed significant alterations in the expression levels of 48 genes in the resistant mice, while by these same criteria, there were seven differentially expressed genes in the susceptible B6.CAST mice. Differentially expressed genes in both groups of mice included subsets of transcription factors. However, only in the resistant mice was there a significant induction of proteins involved in cell-survival pathways such as HSP70, HSP40, p21, GADD45beta, Ier3, and Nf-kappaB. Moreover, increased expression of three of these factors after noise was confirmed at the protein level. Drastically enhanced HSP70, GADD45beta, and p21 immunostaining were detected 6 h after the noise exposure in subsets of cells of the lateral wall, spiral limbus, and organ of Corti as well as in cochlear nerve fibers. Upregulation of these proteins after noise exposure likely contributes to the prevalence of survival cellular pathways and thus to the resistance to NIHL that is characteristic of the 129X1/SvJ mice.
Publication Title
Noise-induced changes in gene expression in the cochleae of mice differing in their susceptibility to noise damage.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 12 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Temporal changes in the embryo transcriptome between the blastocyst stage (Day 7) and initiation of elongation (Day 13) differ between in vivo- and in vitro-derived embryos and are reflective of subsequent developmental fate.
Publication Title
Transcriptome changes at the initiation of elongation in the bovine conceptus.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 15 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
The aim of this study was to compare the transcriptome of the different regions of the oviduct between pregnant and cyclic heifers. After synchronizing crossbred beef heifers, those in standing oestrus (=Day 0) were randomly assigned to cyclic (non bred, n=6), or pregnant (artificially inseminated, n=11) groups. They were slaughtered on Day 3 and both oviducts from each animal were isolated and cut in half to separate ampulla and isthmus. Each portion was flushed to confirm the presence of an oocyte/embryo and was then opened longitudinally and scraped to obtain epithelial cells which were snap-frozen. Oocytes and embryos were located in the isthmus of the oviduct ipsilateral to the corpus luteum. Microarray analysis of oviductal cells revealed that proximity to the corpus luteum did not affect the transcriptome of the isthmus, irrespective of pregnancy status. However, 2287 genes were differentially expressed (P<0.01) between the ampulla and isthmus of the oviduct ipsilateral to the corpus luteum. Gene ontology revealed that the main biological processes overrepresented in the isthmus were synthesis of nitrogen, lipids, nucleotides, steroids and cholesterol as well as vesicle-mediated transport, cell cycle, apoptosis, endocytosis and exocytosis, whereas cell motion, motility and migration, DNA repair, calcium ion homeostasis, carbohydrate biosynthesis and regulation of cilium movement and beat frequency were overrepresented in the ampulla. In conclusion, large differences in gene expression were observed between the isthmus and ampulla that reflect morphological and functional characteristics of each segment.
Publication Title
Spatial differences in gene expression in the bovine oviduct.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 10 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
In cattle, almost all fully grown vesicle stage oocytes (GV) have the ability to resume meisos, develop to Metaphase II stage (MII), support fertilization and progress through the early embryonic cycles in vitro. Yet without intensive selection, the majority fail to develop to the blastocyst stage.
Publication Title
Sequential analysis of global gene expression profiles in immature and in vitro matured bovine oocytes: potential molecular markers of oocyte maturation.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
The objective of this study was to examine the effect of the presence of a single or multiple embryo(s) on the transcriptome of the bovine oviduct. In Experiment 1, cyclic (non-bred, n = 6) and pregnant (artificially inseminated, n = 11) heifers were slaughtered on Day 3 after estrus, and the ampulla and isthmic regions of the oviduct ipsilateral to the corpus luteum were separately flushed. Oviductal epithelial cells from the isthmus region, in which all oocytes/embryos were located, were snap-frozen for microarray analysis. In Experiment 2, heifers were divided into cyclic (non-bred, n = 6) or pregnant (multiple embryo transfer, n = 10) groups. In vitro-produced presumptive zygotes were transferred endoscopically to the ipsilateral oviduct on Day 1.5 post estrus (n = 50 zygotes per heifer). Heifers were slaughtered on Day 3 and oviductal isthmus epithelial cells were recovered for RNA sequencing. Microarray analysis in Experiment 1 failed to detect any difference in the transcriptome of the oviductal isthmus induced by the presence of a single embryo. In Experiment 2, following multiple embryo transfer, RNA sequencing revealed 278 differentially expressed genes of which 123 were up- and 155 were down-regulated in pregnant heifers. Most of the down-regulated genes were related to immune function. Overall design: Transcriptional profiles of oviductal isthmus epithelial cells from cyclic and pregnant heifers were generated by sequencing of total RNA on the Illumina HiSeq 2500 platform
Publication Title
Oviduct-Embryo Interactions in Cattle: Two-Way Traffic or a One-Way Street?
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Bos taurus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Oviduct-Embryo Interactions in Cattle: Two-Way Traffic or a One-Way Street?
Sample Metadata Fields
Specimen part, Treatment
View Samples- Bos taurus
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
The objective of this study was to examine the effect of the presence of a single or multiple embryo(s) on the transcriptome of the bovine oviduct. In Experiment 1, cyclic (non-bred, n = 6) and pregnant (artificially inseminated, n = 11) heifers were slaughtered on Day 3 after estrus, and the ampulla and isthmic regions of the oviduct ipsilateral to the corpus luteum were separately flushed. Oviductal epithelial cells from the isthmus region, in which all oocytes/embryos were located, were snap-frozen for microarray analysis. In Experiment 2, heifers were divided into cyclic (non-bred, n = 6) or pregnant (multiple embryo transfer, n = 10) groups. In vitro-produced presumptive zygotes were transferred endoscopically to the ipsilateral oviduct on Day 1.5 post estrus (n = 50 zygotes per heifer). Heifers were slaughtered on Day 3 and oviductal isthmus epithelial cells were recovered for RNA sequencing. Microarray analysis in Experiment 1 failed to detect any difference in the transcriptome of the oviductal isthmus induced by the presence of a single embryo. In Experiment 2, following multiple embryo transfer, RNA sequencing revealed 278 differentially expressed genes of which 123 were up- and 155 were down-regulated in pregnant heifers. Most of the down-regulated genes were related to immune function.
Publication Title
Oviduct-Embryo Interactions in Cattle: Two-Way Traffic or a One-Way Street?
Sample Metadata Fields
Specimen part
View Samples