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GSE21912
Homo sapiens
37 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The RPMI-8226 human multiple myeloma cell line was stably infected with either a validated shRNA against BMI1 or a control shRNA. RNA was prepared from these lines, +/- doxycycline induction and at various time points post-induction. Samples were hybridized on the Affymetrix U133plus2 human genome expression microarray.
Publication Title
The Polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Bmi-1 and Mel-18 are close structural homologues that belong to the polycomb group (PcG) of transcriptional regulators of homeotic gene expression in development. They are believed to stably maintain repression of gene expression by altering the state of chromatin at specific promoters. A number of clinical and experimental observations have also implicated Bmi-1 in tumorigenesis and stem cell maintenance. Bmi-1 overexpression or amplification has been observed in a number of human malignancies, particularly in B-cell lymphomas, medulloblastomas and breast cancer. We report here that shRNA-mediated knock-down of either Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of proliferation, loss of clonogenic survival and anchorage-independent growth, and suppression of xenograft tumor formation in nude mice. Furthermore, overexpression of both Bmi-1 and Mel-18 significantly increased clonogenic survival of Rat1 fibroblasts. In contrast, stable downregulation of Bmi-1 or Mel-18 alone did not affect the growth of SK-OV-3 or U2OS cancer cell lines or normal human WI38 fibroblasts. Gene expression analysis of shRNA-expressing DAOY cells has demonstrated a significant overlap in the Bmi-1- and Mel-18-regulated genes and revealed novel gene targets under their control. Taken together, these results suggest that Bmi-1 and Mel-18 might have overlapping functions in human tumorigenesis.
Publication Title
Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mutations in Hedgehog (Hh) pathway genes, leading to constitutive activation of Smoothened (Smo), occur in sporadic medulloblastoma, the most common brain cancer in children. Antagonists of Smo induce tumor regression in mouse models of medulloblastoma and hold great promise for targeted therapy for this tumor. However, acquired resistance has emerged as one of the major challenges of targeted cancer therapy. Here, we describe novel mechanisms of acquired resistance to Smo antagonists in medulloblastoma. NVP-LDE225, a potent and selective Smo antagonist, inhibits Hh signaling and induces tumor regressions in allograft models of medulloblastoma that are driven by mutations of Patched (Ptch), a tumor suppressor in the Hh pathway. However, after long-term treatment, evidence of acquired resistance was observed. Genome-wide profiling of resistant tumors revealed distinct mechanisms to evade the inhibitory effects of Smo antagonists. Chromosomal amplification of Gli2, a downstream effector of Hh signaling, reactivated Hh signaling and restored tumor growth. Analysis of pathway gene-expression signatures selectively deregulated in resistant tumors identified increased phosphoinosite-3-kinase (PI3K) signaling as another potential resistance mechanism. Probing the functional relevance of increased PI3K signaling, we showed that the combination of NVP-LDE225 with the dual PI3K/mTOR inhibitor NVP-BEZ235 markedly delayed the development of resistance. Our findings have important clinical implications for future treatment strategies in medulloblastoma.
Publication Title
Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Abstract Background Traumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24h post-injury. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and nave (control) brain tissue were used for microarray analysis. Ingenuity Pathway Analysis (IPA) software was used to identify molecular pathways and networks that were associated with the altered gene expression in brain tissues following TBI. Results Inspection of the top fifteen biological functions in IPA associated with TBI in the ipsilateral tissues revealed that all had an inflammatory component. IPA analysis also indicated that inflammatory genes were altered on the contralateral side, but many of the genes were inversely expressed compared to the ipsilateral side. The contralateral gene expression pattern suggests a remote anti-inflammatory molecular response. We created a network of the inversely expressed common (i.e., same gene changed on both sides of the brain) inflammatory response (IR) genes and those IR genes included in pathways and networks identified by IPA that changed on only one side. We ranked the genes by the number of direct connections each had in the network, creating a gene interaction hierarchy (GIH). Two well characterized signaling pathways, toll-like receptor/NF-kappaB signaling and JAK/STAT signaling, were prominent in our GIH. Conclusions Bioinformatic analysis of microarray data following TBI identified key molecular pathways and networks associated with neural injury following TBI. The GIH created here provides a starting point for investigating therapeutic targets in a ranked order that is somewhat different than what has been presented previously. In addition to being a vehicle for identifying potential targets for post-TBI therapeutic strategies, our findings can also provide a context for evaluating the potential of therapeutic agents currently in development.
Publication Title
Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response.
Sample Metadata Fields
Specimen part, Treatment
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
- 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- Bos taurus
- 35 Downloadable Samples
- NextSeq 500
Description
This study relates to embryo-maternal interaction. The aim was to compare the transcriptome and ability of the ipsilateral and contralateral uterine horns to support preimplantation conceptus survival and growth to Day 14. Although differences in gene expression exist between the endometrium of uterine horns ipsilateral and contralateral to the CL in cattle, they do not impact conceptus survival or length between Days 7 and 14. Overall design: The endometrial samples from both uterine horns were collected from synchronized heifers slaughtered on Day 5, 7, 13 or 16 post-estrus (n = 5 per time) and subjected to RNA sequencing.
Publication Title
Do differences in the endometrial transcriptome between uterine horns ipsilateral and contralateral to the corpus luteum influence conceptus growth to day 14 in cattle?
Sample Metadata Fields
Specimen part, Subject, Time
View Samples