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SRP070849
Mus musculus
19 Downloadable Samples
Illumina HiSeq 2000
Description
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH. Functional studies have shown these mutations contribute to transformation, although how these mutations impact the response to epigenetic therapies is not fully delineated. Here we show AMLs with TET2/IDH2 mutations combined with FLT3ITD mutations are specifically sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine/AG-221 therapies induced a reduction in leukemic blasts and in stem/progenitor expansion, with attenuation of aberrant DNA hypermethylation. These therapeutic benefits were achieved through restoration of differentiation, such that normalized hematopoiesis was derived from mutant cells. Consistent with these data, at the time of clinical response to 5-Azacytidine or AG-221, most patients had mutant-derived hematopoiesis. By contrast, combined AG-221/5-Azacytidine plus FLT3 inhibition reduced disease burden and reversed epigenetic dysfunction. Our studies suggest combined targeting of signaling and epigenetic pathways can increase therapeutic response in AML. Overall design: We profiled genome-wide transcription patterns of the hematopoietic stem cells (LSK) population in Wild-type, Idh2 R140Q Flt3-ITD, and Tet2-/-;Flt3-IDT mice. Idh2 R140Q Flt3-ITD mice with AML were treated with either vehicle or AG-221 (the first small molecule in vivo inhibitor of IDH2 to enter clinical trials). Tet2-/-;Flt3-IDT mice with AML were treated with vehicle or 5-Azacytidine (Decitabine, hypomethylating agent).
Publication Title
Combination Targeted Therapy to Disrupt Aberrant Oncogenic Signaling and Reverse Epigenetic Dysfunction in <i>IDH2</i>- and <i>TET2</i>-Mutant Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Schizosaccharomyces pombe
- 5 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Positioned nucleosomes limit the access of proteins to DNA and implement regulatory features encoded in eukaryotic genomes. Here we generated the first genome-wide nucleosome positioning map for Schizosaccharomyces pombe and annotated transcription start and termination sites genome-wide. Using this resource we found surprising differences compared to the nucleosome organization in the distantly related yeast Saccharomyces cerevisiae [the cerevisiae data has been published by others (PMID: 17873876) and the raw data is deposited at ArrayExpress(E-MEXP-1172)]. DNA sequence guides nucleosome positioning differently, e.g., poly(dA:dT) elements are not enriched in S. pombe nucleosome-depleted regions (NDRs). Regular nucleosomal arrays emanate more asymmetrically, i.e., mainly co-directionally with transcription, from promoter NDRs, but promoters harbouring the histone variant H2A.Z show regular arrays also upstream. Regular nucleosome phasing in S. pombe has a very short repeat length of 154 base pairs, and requires a remodeler, Mit1, conserved in humans but not found in S. cerevisiae. Nucleosome positioning mechanisms are evidently not universal but evolutionarily plastic.
Publication Title
Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
mRNA expression profiling of pancreatic cancer, comparing adjacent normal tissue, patient tumour and first generation patient derived xenograft tumours
Publication Title
Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Gene expression of mouse hepatoblasts (HBs) expressing IDH1 WT, IDH1 R132C, IDH2 WT, R172K and empty vector controls (N=2 cultures for each condition) grown on collagen-coated plates and IDH1 R132C and empty vector controls on uncoated plates were evaluated using Affymetrix Mouse 430Av2 DNA microarrays that were processed at the Dana-Farber Cancer Institute core facility (http://macf-web.dfci.harvard.edu/) using their standard protocol.
Publication Title
Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Total RNA was isolated from proliferating and senescent IMR90 cells to compare gene-expression to the changes in nucleolus-association in proliferating and senescent IMR90 cells.
Publication Title
Nucleolus association of chromosomal domains is largely maintained in cellular senescence despite massive nuclear reorganisation.
Sample Metadata Fields
Specimen part
View Samples- Populus tremula x populus alba
- 4 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
We studied differences in gene expression between Populus P35S::EBB1 lines and control, affecting plant growth and differentiation, and dormancy. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes driven by overexpression of the EBB1 gene.
Publication Title
EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees.
Sample Metadata Fields
Specimen part
View Samples- Populus tremula x populus alba
- 2 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
We study gene expression Populus amiEBB1 lines affecting dormancy. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes droved by expression of artifical micro RNA (ami) targeting EBB1 gene.
Publication Title
EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Expression data from HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa treated with DMSO or medium with low LDL
Publication Title
Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants regulate their time to flowering by gathering information from the environment. Photoperiod and temperature are among the most important environmental variables. Suboptimal, but not near-freezing, temperatures regulate flowering through the thermosensory pathway, which overlaps with the autonomous pathway. Here we show that ambient temperature regulates flowering by two genetically distinguishable pathways, one that requires TFL1 and another that requires ELF3. The delay in flowering time observed at lower temperatures was partially suppressed in single elf3 and tfl1 mutants, whereas double elf3 tfl1 mutants were insensitive to temperature. tfl1 mutations abolished the temperature response in cryptochrome mutants that are deficient in photoperiod perception, but not in phyB mutants that have a constitutive photoperiodic response. Contrary to tfl1, elf3 mutations were able to suppress the temperature response in phyB mutants, but not in cryptochrome mutants. The gene expression profile revealed that the tfl1 and elf3 effects are due to the activation of different sets of genes and identified CCA1 and SOC1/AGL20 as being important cross talk points. Finally, genome-wide gene expression analysis strongly suggests a general and complementary role for ELF3 and TFL1 in temperature signalling.
Publication Title
A complementary role for ELF3 and TFL1 in the regulation of flowering time by ambient temperature.
Sample Metadata Fields
No sample metadata fields
View Samples- Populus tremula x populus alba
- 10 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
Regeneration of transgenic cells remains a major obstacle to research and commercial deployment of transgenic plants for most species.
Publication Title
Genome scale transcriptome analysis of shoot organogenesis in Populus.
Sample Metadata Fields
Sex
View Samples