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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- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Using the ED-L2 promoter of Epstein-Barr virus to drive Cre, we obtained tissue specific ablation of Klf4 in the squamous epithelia of the esophagus.
Publication Title
Esophageal squamous cell dysplasia and delayed differentiation with deletion of krüppel-like factor 4 in murine esophagus.
Sample Metadata Fields
Sex, Age, 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- Mus musculus
- 16 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Our studies identify a mechanism of signaling crosstalk during valve morphogenesis that sheds light on the origin of congenital heart defects associated with reduced Notch function. Overall design: Aortic and pulmonary cardiac valves were isolated by laser microdissection from WT and Jag1flox;Nkx2.5-Cre mouse embryos at stage E14.5, and their expression profile characterized by RNA-Seq.
Publication Title
Sequential Ligand-Dependent Notch Signaling Activation Regulates Valve Primordium Formation and Morphogenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
Description
Aim: to perform a genome-wide investigation of chromatin landscape and gene expression patterns downstream of calcium and kinase signaling in Jurkat T cells. Methods: PMA and ionomycin were used to activate the calcium and kinase signalling networks involved in T cell activation. Global gene expression was measured using RNA-seq, whilst ATAC-seq was used to probe chromatin landscape following 3 hours of stimulation with PMA, ionomycin or both. All experiments were performed in triplicate. For RNA-seq all sequencing was performed using paired-end sequencing on an Illumina HiSeq2500 instrument. For ATAC-seq sequencing was performed using a HiSeq 1500. Results: we mapped approximately 60 million reads per sample for ATAC-seq, and 22 million reads per library for RNA-seq. Overall we identified 57,825 transcripts and 19,763 ATAC-seq peaks. We identifiead 1648 genes whose expression was increased by 2-fold or more by at least one treatment in comparison to untreated cells. Similarly, we identified 3972 ATAC peaks that were induced by at least 2-fold by treatment in comparison to untreated cells. Conclusions: we found that chromatin landscape was associated with gene expression downstream of calcium and kinase signaling in Jurkat cells. Further to this we found that activation of the full complement of TCR-responsive genes is dependent upon both PMA and ionomycin, and amounts to more than just the sum of both. Overall design: RNA-sequencing and ATAC-sequencing were performed after 3 hours of treatment with either PMA, ionomycin or co-treatment with PMA and ionomycin.
Publication Title
Integration of Kinase and Calcium Signaling at the Level of Chromatin Underlies Inducible Gene Activation in T Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 332 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 109 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Global microarray (HG U133 Plus 2.0) was used to investigate the effects of resistance exercise and resistance training on the skeletal muscle transcriptome profile of 28 young and old adults. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Publication Title
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Global microarray (HG U133 Plus 2.0) was used for the first time to investigate the effects of resistance exercise on the transcriptome in slow-twitch myosin heavy chain (MHC) I and fast-twitch MHC IIa muscle fibers of young and old women. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Publication Title
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Global microarray (HG U133 Plus 2.0) was used to investigate the basal level skeletal muscle transcriptome profile of young and old adults. One vastus lateralis muscle biopsy was obtained in the basal state from 36 different subjects.
Publication Title
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
We used RNA sequencing to identify differentially expressed genes during esophageal epithelial differentiation and in the presence of interleukin 13 using an air-liquid interface culture system. Overall design: RNA sequencing was performed on a human esophageal epithelial cell line (EPC2-hTERT) grown submerged (day 8) or at the air-liquid interface (ALI) (day 14, untreated or treated with interleukin 13 [100 ng/mL])
Publication Title
Eosinophilic esophagitis-linked calpain 14 is an IL-13-induced protease that mediates esophageal epithelial barrier impairment.
Sample Metadata Fields
No sample metadata fields
View Samples