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SRP050061
Homo sapiens
6 Downloadable Samples
IlluminaHiSeq2000
Description
Total RNA extracted from prostate cancer LNCaP cells transfected with siRNA against CTCF(siCTCF), or negative control siRNA (si-)were processed, and sequenced by two different companies using Illumina Hi-seq 2000 platform to generate RNA sequencing with two output sequences: paired-end 50bp and 101bp in read length. Nearly 100 million and 50 million raw reads were yielded from each sample respectively. We used FastQC to confirm the quality of raw fastq sequencing data, and SOAPfuse software to detect fusion transcripts. Overall design: Discovering fusion genes from siCTCF and si- in LNCaP cells.
Publication Title
Discovery of CTCF-sensitive Cis-spliced fusion RNAs between adjacent genes in human prostate cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- NextSeq 500
Description
Increasing fetal hemoglobin (HbF) levels in adult red blood cells provides clinical benefit to patients with sickle cell disease and some forms of beta-thalassemia. To identify potentially druggable HbF regulators in adult human erythroid cells, we employed a protein kinase-domain focused CRISPR/Cas9-based genetic screen with a newly optimized sgRNA scaffold. The screen uncovered the heme-regulated inhibitor HRI (also known as EIF2AK1), an erythroid-specific kinase that controls protein translation, as an HbF repressor. HRI depletion markedly increased HbF production in a specific manner and reduced sickling in cultured erythroid cells. Diminished expression of the HbF repressor BCL11A accounted in large part for the effects of HRI depletion. Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies. Overall design: A CRISPR-screen reveals HRI kinase as a fetal hemoglobin repressor and further validated in HUDEP2 and CD34+ derived primary erythroid cultures.
Publication Title
Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 47 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The aim of this study was to measure the influence of beverages on blood gene expression. We wanted to explore the underlying mechanisms of the cardioprotective effects of red wine.
Publication Title
Analysis with respect to instrumental variables for the exploration of microarray data structures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
HMGN1 contributes to the shortened latency of liver tumorigenesis by changing a chromatin structure and expression of relevant genes
Publication Title
Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 108 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Transcriptomic changes in human liver cancer cell lines caused by the demethylating drug zebularine.
Publication Title
An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 32 Downloadable Samples
Description
Although epigenetic mechanisms, such as specific histone modifications, control common and cell-specific genetic programs, a role for histone modifying enzymes in liver metabolism and disease has not been investigated. This report demonstrates that the combined loss of the histone methyltransferases EZH1 and EZH2 in mouse hepatocytes led to the disruption of H3K27me3 homeostasis by age three months, simple fatty liver by age six months and fatal fibrosis by age 15 months. Global and gene-specific reduction of H3K27me3 marks paralleled a concomitant increase of H3K4me3 marks at genes associated with chronic liver disease. Advanced disease was accompanied by widespread infiltration of immune cells, an increase of activated hepatic stellate cells and collagen deposition. Expression of genes from the cytochrome P450 family that control drug metabolism was already deregulated by age two months and mice were fatally hypersensitive to carbon tetrachloride (CCl4). These genetic experiments, for the first time, illustrate that the simple loss of EZH1/EZH2, which results in the disruption of epigenetic modifications, is sufficient for the progression of fatal liver disease. Overall design: RNA-seq and ChIP-seq were performed in liver tissues.
Publication Title
The methyltransferases enhancer of zeste homolog (EZH) 1 and EZH2 control hepatocyte homeostasis and regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The tumor suppressor BRCA1 regulates DNA damage responses and multiple other processes. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal RING domain. Here we show that BRCA1 promotes oxidative metabolism via degradation of Oct1, a transcription factor with pro-glycolytic/tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells towards a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNAseq confirms the deregulation of metabolic genes. BRCA1 mediates direct Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenografts. Oct1 protein levels correlate positively with tumor aggressiveness, and inversely with BRCA1, in primary breast cancer samples. These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1 degradation to promote oxidative metabolism. Overall design: mRNA profiles of BRCA1-I26A mutant MEFs treated with control CRISPR lentiviral vector, or an Oct1-specific CRISPR construct
Publication Title
BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and Carbohydrate Metabolism.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B cell dysfunction due to unspecific B cell activation. How HIV-1 affects antigen-specific B cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T cell - B cell immune synapse. This interference reduced B cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
Publication Title
HIV-1 infection of CD4 T cells impairs antigen-specific B cell function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global program of gene expression underlying the effect of p17 on human plasmacytoid dendritic cells and was compared to CpG profile.
Publication Title
HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphologyical and global gene expression profile molecular features consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into induced multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelinmyelinating axons both in vitro and in vivo. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.
Publication Title
Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples