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SRP042158
Homo sapiens
42 Downloadable Samples
Illumina HiSeq 2500
Description
Transcriptome analysis was conducted on vorinostat resistant HCT116 cells (HCT116-VR) upon knockdown of potential vorinostat resistance candidate genes in the presence and absence of vorinostat. Potential vorinostat resistance candidate genes chosen for this study were GLI1 and PSMD13, which were identified through a genome-wide synthetic lethal RNA interference screen. To understand the transcriptional events underpinning the effect of GLI1 and PSMD13 knockdown (sensitisation to vorinostat-induced apoptosis), cells were first subjected to gene knockdown, then to treatment with vorinsotat or the solvent control. Two timepoints for drug treatment were assessed: a timepoint before induction of apoptosis (4hrs for siGLI1 and 8hrs for siPSMD13) and a timepoint when apoptosis could be detected (8hrs for siGLI1 and 12hrs for siPSMD13). Overall design: There are 42 samples in total, from triplicate independent biological experiments of 14 samples each.
Publication Title
A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
Here, we analyzed two small RNA libraries derived from ovarian tissue mutant for either the Drosophila SETDB1 gene, or the Bam gene. Here we show that deposition of histone 3 lysine 9 by the methyltransferase dSETDB1 (egg) is required for piRNA cluster transcription. In the absence of dSETDB1, cluster precursor transcription collapses in germline and somatic gonadal cells and TEs are activated, resulting in germline loss and a block in germline stem cell differentiation. We propose that heterochromatin protects the germline by activating the piRNA pathway. Keyword : Epigenetics Overall design: 2 libraries were analyzed, with 1 being a developmental control (Bam Mutant).
Publication Title
piRNA production requires heterochromatin formation in Drosophila.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Targeting BET bromodomain proteins utilizing small molecules in an emerging anti-cancer strategy with clinical evaluation of at least six inhibitors now underway. While MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional anti-tumor activities are important. Using the Eµ-Myc model of B-cell lymphoma we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of pro-apoptotic (Bim) and anti-apoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent with this, Bim knockout or Bcl-2 overexpression inhibited apoptosis induction by JQ1. We identified lymphomas that were either intrinsically resistant to JQ1-mediated death or acquired resistance following in vivo exposure. Strikingly, in both instances BCL-2 was strongly upregulated and was concomitant with activation of RAS pathways. Eµ-Myc lymphomas engineered to express activated Nras upregulated BCL-2 and acquired a JQ1-resistance phenotype. These studies provide important information on mechanisms apoptosis induction and resistance to BET-inhibition, while providing further rationale for the translation of BET inhibitors in aggressive B-cell lymphomas. Overall design: RNA-Sequencing of JQ1 resistant and sensitive Eµ-Myc cell lines
Publication Title
BET Inhibition Induces Apoptosis in Aggressive B-Cell Lymphoma via Epigenetic Regulation of BCL-2 Family Members.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by tet-regulated MLL-AF9 co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in Tet-Off MLL-AF9 AML cells in vitro partially phenocopies MLL-AF9 depletion and results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. To compare gene expression changes associated with enforced Id2 expression and MLL-AF9 withdrawal, RNA sequencing analysis was performed on Tet-off MLL-AF9 cells transduced with an Id2 over-expressing or a control vector, or upon MLL-AF9 dox-inducible knock-down. Overall design: Primary AMLs driven by Tet-off inducible MLL/AF9 expression linked to dsRED reporter, in association with oncogenic NRASG12D (Tet-off MLL-AF9) were generated by reconstituting lethally irradiated congenic mice with foetal liver cells co-transduced with a Tet-Off-MLL-AF9-dRED retroviral vector and a second vector co-expressing NRASG12D together with the Tet-Off responsive transcriptional activator. RNA sequencing analysis sequencing analysis was performed on Tet-Off MLL-AF9/dsRED+ AML cells treated in vitro with doxycycline (DOX) for 4 days to inactivate MLL-AF9 expression or left untreated (UT). For the Id2 over-expression experiment, Tet-Off MLL-AF9/dsRED+ AML cells were transduced in vitro with an Id2-GFP or a control-GFP retroviral vector. Viable GFP-positive cells were FACS-sorted 2 days after transduction and used for RNA sequencing analysis.
Publication Title
Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an Id2/GFP-reporter mouse model of MLL-AF9-driven AML, we showed that Id2 is expressed heterogeneously across the leukemic population. Moreover, differential expression of Id2 and the stemness marker Kit defines subsets of AML cells with different leukemogenic properties with lower levels of Id2 associated with enrichment in leukemia stem cell potential. To define gene expression patterns associated with distinct endogenous levels of Id2 and higher LSC potential, RNA sequencing analysis was performed on FACS-sorted KitHI–Id2HI (BM_Kplus-Iplus), KitHI–Id2LOW(BM_Kplus-Iminus), KitLOW–Id2HI (BM_Kminus-Iplus) and KitLOW–Id2LOW (BM_Kminus-Iminus) MLL-AF9-cherry+ AML cells obtained from bone marrow of terminally sick mice. Overall design: Primary MLL-AF9+ AMLs were generated by reconstituting lethally irradiated congenic mice with foetal liver cells obtained from Id2-GFP reporter mice and transduced with a retroviral vector co-expressing MLL-AF9 and the cherry reporter protein. KitHigh–Id2High, KitHigh–Id2Low, KitLow–Id2High and KitLow–Id2Low MLL-AF9/cherry+ AML cells obtained from bone marrow of terminally sick primary recipients were FACS-sorted and used for RNA sequencing analysis (3 samples/subset).
Publication Title
Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
We investigated the role of the transcriptional regulators Id2 and E2-2 (encoded by Tcf4) in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by a Tet-off inducible MLL-AF9 allele co-expressed with oncogenic NRASG12D, we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in MLL-AF9 AML cells results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. E2-2 silencing phenocopies Id2 overexpression in MLL-AF9-AML cells. To study the gene expression changes associated with E2-2 depletion in the context of MLL-rearranged AML, RNA sequencing analysis was performed on MLL-AF9;NRAS AML cells transduced with vectors expressing hairpins against E2-2 (shTcf4#654 and shTcf4#3646) or a control hairpin against Renilla luciferase (shRen). Overall design: Primary AMLs driven by MLL/AF9 expression linked to cherry reporter, in association with oncogenic NRASG12D (MLL/AF9;NRAS) were generated by reconstituting lethally irradiated congenic mice with fetal liver cells co-transduced with the MSCV-MLL/AF9-IRES-cherry retroviral vector and a second vector co-expressing NRASG12D together with luciferase (MSCV-luciferase-IRES-NRASG12D). RNA sequencing analysis sequencing analysis was performed on MLL-AF9;NRAS AML cells transduced in vitro with vectors expressing hairpins against E2-2 (shTcf4#654 and shTcf4#3646) or a control hairpin against Renilla luciferase (shRen) linked to the reporter GFP. Viable GFP-positive cells were FACS-sorted 2 days after transduction and used for RNA sequencing analysis. Two independent biological replicates of the experiment were used for the RNA sequencing (9-5-14 and 14-4-14).
Publication Title
Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In exploring mechanisms, we found the Ets transcription family member Etv5/Erm is strongly regulated by MEK. Our microarray assay showed that Erm is specifically downregulated in Mek mutant brain.
Publication Title
MEK Is a Key Regulator of Gliogenesis in the Developing Brain.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Inactivation of ERK/MAPK signaling in developing postmitotic cortical excitatory neurons results in a significent loss of Ctip2 positive layer 5 neurons and axon projections. Microarray dada revealed the reduced levels of a vast majority of layer V specific transcripts.
Publication Title
Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Affymetrix human whole transcriptome array (HTA 2.0) completed on patients with Crohn's disease undergoing their first ileocolic resection
Publication Title
Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected].
Sample Metadata Fields
Specimen part, Treatment
View Samples