Filters
Technology
Platform
GSE92619
Homo sapiens
40 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Activated B-cell-like (ABC) and germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL) represent the two major molecular DLBCL subtypes. They are characterized by differences in clinical course and by divergent addiction to oncogenic pathways. To determine activity of novel compounds in these two subtypes, we conducted an unbiased pharmacologic in vitro screen. The phosphatidylinositol-3-kinase (PI3K) alpha/delta (PI3Ka/d) inhibitor AZD8835 showed marked potency in ABC DLBCL models, whereas the protein kinase B (AKT) inhibitor AZD5363 induced apoptosis in PTEN-deficient DLBCLs. These in vitro results were confirmed in various cell line xenograft and patient-derived xenograft mouse models in vivo. Treatment with AZD8835 induced inhibition of nuclear factor kappa-B (NF-kB) signaling, prompting us to combine AZD8835 with the Brutons tyrosine kinase (BTK) inhibitor ibrutinib. This combination was highly synergistic and effective both in vitro and in vivo. In contrast, the AKT inhibitor AZD5363 was effective in PTEN-deficient DLBCLs through downregulation of the oncogenic transcription factor MYC. Collectively our data suggest that patients should be stratified according to their oncogenic dependencies when treated with PI3K and AKT inhibitors.
Publication Title
Sensitivity to PI3K and AKT inhibitors is mediated by divergent molecular mechanisms in subtypes of DLBCL.
Sample Metadata Fields
Cell line, Treatment
View Samples- Populus trichocarpa
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
Illumina HiSeq2000 technology was used to generate mRNA profiles from the ectomycorrhizal fungi Laccaria bicolor colonizing roots of Populus trichocarpa. Samples were taken after 3 months of contact in order to identify mycorrhiza-regulated transcripts. 100bp reads were generated and aligned to the Populus trichocarpa (http://www.phytozome.net/poplar.php) reference genome. Overall design: mRNA profiles from Populus trichocarpa roots colonized by Laccaria bicolor for three months as well as from control roots were generated by using one lane of 1X100bp Illumina HiSeq2000 sequencing per sample.
Publication Title
Populus trichocarpa encodes small, effector-like secreted proteins that are highly induced during mutualistic symbiosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Populus tremula x populus tremuloides, Populus tremula x populus alba
- 14 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
We conducted microarray experiments by comparing constitutive and inducible Flowering Locus T1 (FT1) and FT2 constructs with appropriate controls, followed by the identification of common targets of Pro35S:FT1 and ProHSP:FT1 or Pro35S:FT2 and ProHSP:FT2.
Publication Title
FLOWERING LOCUS T duplication coordinates reproductive and vegetative growth in perennial poplar.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Post-transcriptional gene regulation by miRNAs and RNA binding proteins (RBP) is important in development, physiology and disease. To examine the interplay between miRNAs and the RBP ELAVL1 (a.k.a. HuR), we mapped miRNA binding sites on a transcriptome-wide scale in WT and Elavl1 knockout murine bone marrow-derived macrophages. Proximity of ELAVL1 binding sites attenuated miRNA binding to transcripts and promoted gene expression. Transcripts that regulate angiogenesis and macrophage/ endothelial cross talk were preferentially targeted by miRNAs, suggesting that ELAVL1 promotes angiogenesis, at least in part, by antagonism of miRNA function. We found that ELAVL1 antagonized binding of miR-27 to the 3'UTR of Zfp36 mRNA and alleviated miR-27-mediated suppression of the RBP ZFP36 (a.k.a. Tristetraprolin). Thus the miR-27-regulated mechanism synchronizes the expression of ELAVL1 and ZFP36. This study provides a resource for systems-level interrogation of post-transcriptional gene regulation in macrophages, a key cell type in inflammation, angiogenesis and tissue homeostasis. Overall design: Bone marrow derived macrpohges mRNA profiles of 7-day cultured wild type (WT) and Elavl1l-/- mouse bone marrow cells were generated by deep sequencing, with 4 biologic duplication, using Illumina GAII.
Publication Title
ELAVL1 modulates transcriptome-wide miRNA binding in murine macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 56 Downloadable Samples
- Illumina HiSeq 2500
Description
Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. While conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors (CLP). Here we found that pDCs developed predominantly from IL7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, while pDC identity relies on TCF4. RNA sequencing of IL7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed by single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen. Overall design: Bulk RNA Seq was performed from sort purified DN, SP and DP lymphoid progenitors and BM pDCs of 4 individual mice
Publication Title
Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. While conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors (CLP). Here we found that pDCs developed predominantly from IL7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, while pDC identity relies on TCF4. RNA sequencing of IL7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed by single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen. Overall design: BM and splenic pDCs were sorted from 3 mice and 3000 cells/sample were used for single cell RNA Seq (10x genomics)
Publication Title
Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina Genome Analyzer
Description
Regional identity of several kind of human neural stem cells were assessed by RNA-Seq Overall design: We compared whole transcriptome of human fetal spinal cord, fetal brain, fetal spinal cord derived NSCs, H9-derived NSCs, H9-derived spinal cord NSCs, and UCSF4-derived spinal cord NSCs
Publication Title
Generation and post-injury integration of human spinal cord neural stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide catalytic sequence-specific cleavage of fully or nearly fully complementary target mRNAs or control translation and/or stability of many mRNAs that share 6-8 nucleotides (nt) of complementarity to the siRNA and miRNA 5' end. siRNA- and miRNA-containing ribonucleoprotein silencing complexes are assembled from double-stranded 21- to 23-nt RNase III processing intermediates that carry 5' phosphates and 2-nt overhangs with free 3' hydroxyl groups. Despite the structural symmetry of a duplex siRNA, the nucleotide sequence asymmetry can generate a bias for preferred loading of one of the two duplex-forming strands into the RNA-induced silencing complex (RISC). Here we show that the 5'-phosphorylation status of the siRNA strands also acts as an important determinant for strand selection. 5'-O-methylated siRNA duplexes refractory to 5' phosphorylation were examined for their biases in siRNA strand selection. Asymmetric, single methylation of siRNA duplexes reduced the occupancy of the silencing complex by the methylated strand with concomitant elimination of its off-targeting signature and enhanced off-targeting signature of the phosphorylated strand. Methylation of both siRNA strands reduced but did not completely abolish RNA silencing, without affecting strand selection relative to that of the unmodified siRNA. We conclude that asymmetric 5' modification of siRNA duplexes can be useful for controlling targeting specificity.
Publication Title
Strand-specific 5'-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Using a novel class of chemically-engineered oligonucleotides, termed "antagomirs", we studied the biological significance of silencing miR-122 in the liver of mice at the mRNA level
Publication Title
Silencing of microRNAs in vivo with 'antagomirs'.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 68 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Assessment of mRNA expression levels in fat biopsies from subcutaneous adipose tissue from unrelated individuals.
Publication Title
A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia.
Sample Metadata Fields
Specimen part
View Samples