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Homo sapiens
16 Downloadable Samples
IlluminaHiSeq2000
Description
p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator. Overall design: MCF10A cells transfected with siRNA against LATS1/2 alone, p53 alone or LATS1/2 and p53 together. Two independent MCF10A batches provided biological replicates
Publication Title
Down-regulation of LATS kinases alters p53 to promote cell migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human Alu repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified new circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched compared to linear controls. By scoring the presence of reverse complementary sequences in human introns we predicted and experimentally validated novel circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyper-editing events. Knockdown of the double-strand RNA editing ADAR1 enzyme significantly and specifically up-regulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA:RNA interactions of introns form larger structures which promote circularization of embedded exons, while ADAR1 antagonizes circRNA expression by melting stems within these interactions. Thus, we assign a new function to ADAR1. Overall design: Examination of 12 samples in different stages of C.elegans development.
Publication Title
Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Liver samples of mice harboring liver-specific deletion of Lats2 (Lats2-CKO) were compared to WT mice.
Publication Title
The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
SRP043115- Mus musculus
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Purpose: Probe the transcriptome-wide changes in the expression pattern between WT and Sertoli-specific Upf2 KO testes Methods: Total RNA were extracted from WT and Sertoli-specific Upf2 KO testes in triplicates and subject to deep-sequencing in Ion Torrent seq platform. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 16,014 transcripts in the retinas of WT and Nrl-/- mice with BWA workflow and 34,115 transcripts with TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 12 of these were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for more than four orders of magnitude and a goodness of fit (R2) of 0.8798. Approximately 10% of the transcripts showed differential expression between the WT and Nrl-/- retina, with a fold change =1.5 and p value <0.05. Altered expression of 25 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to retinal function. Data analysis with BWA and TopHat workflows revealed a significant overlap yet provided complementary insights in transcriptome profiling. Conclusions: Our study represents the first detailed analysis of Upf2-mediated NMD pathway in Sertoli cell development Overall design: Testis mRNA profiling was generated from postnatal day 4 WT and Amh-cKO (Sertoli specific Upf2 KO) testes, in triplicates.
Publication Title
UPF2, a nonsense-mediated mRNA decay factor, is required for prepubertal Sertoli cell development and male fertility by ensuring fidelity of the transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In this study, we use pre-malignant cells from different Cebpa mutant acute myeloid leukemia (AML) models. We have used conditional KO models (CreLoxP) and isolated hematopoietic cells shortly after induction of recombination, in order to look at pre-leukemic cells, which have acquired the first hit, but not yet undergone full malignant transformation.
Publication Title
Lack of the p42 form of C/EBPα leads to spontaneous immortalization and lineage infidelity of committed myeloid progenitors.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina Genome Analyzer
Description
This report not only adds a novel mechanism to the current dogma on achieving global shortening of 3''UTRs, but also unveils a novel function of the NMD pathway in establishing tissue-specific transcriptome identity Overall design: We first generated prospermatogonia-specific Upf2 conditional knockout mice (Ddx4-Cre; Upf2 fl/?, hereafter called Ddx4-KO) by crossing Ddx4-Cre13 with Upf2 floxed.
Publication Title
UPF2-Dependent Nonsense-Mediated mRNA Decay Pathway Is Essential for Spermatogenesis by Selectively Eliminating Longer 3'UTR Transcripts.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone modifications are a key epigenetic mechanism to activate or repress the expression of genes. Data sets of matched microarray expression data and histone modification data measured by ChIP-seq exist, but methods for integrative analysis of both data types are still rare. Here, we present a novel bioinformatic approach to detect genes that are differentially expressed between two conditions putatively caused by alterations in histone modification. We introduce a correlation measure for integrative analysis of ChIP-seq and gene expression data and demonstrate that a proper normalization of the ChIP-seq data is crucial. We suggest applying Bayesian mixture models of different distributions to further study the distribution of the correlation measure. The implicit classification of the mixture models is used to detect genes with differences between two conditions in both gene expression and histone modification. The method is applied to different data sets and its superiority to a naive separate analysis of both data types is demonstrated. This GEO series contains the expression data of the Cebpa example data set.
Publication Title
Integrative analysis of histone ChIP-seq and transcription data using Bayesian mixture models.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Whole fetal livers were collected from mouse fetuses at embryonic day 14.5 (E14.5), and single-cell suspensions were prepared by successive passage through 18-, 21 and 23-gauge needles. Fetal liver cells were maintained in Dulbecco modified Eagle medium (DMEM; Invitrogen) supplemented with 10% fetal bovine serum (FBS; Invitrogen), 100 U/ml penicillin, 100g/ml streptomycin, and 50ng/ml recombinant human thrombopoietin (TPO; Peprotech). After 5 days of culture, megakaryocytes were purified using a discontinuous bovine serum albumin gradient (BSA, SigmaAldrich; 3%, 1.5%, and 0%). Total RNA was isolated with TriReagent (MRC) following manufacturers instructions, and its quality was assessed with ND1000 Nanodrop (Peqlab) and on a 1.5% agarose gel.
Publication Title
miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Translocations involving the MLL genes are frequently found in Acute Myeloid Leukemia (AML) and are associated with poor prognosis. The MLL fusion proteins act as aberrant transcription factor activating a transcriptional program that transforms the cells, potentially through collaboration with other transcription factors. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBP to be up-regulated in the AML samples, suggesting that C/EBP might collaborate with MLL fusion proteins in the initial transformation process. We could show that transformation by MLL fusion proteins is dependent on C/EBP activity both in early progenitors as well as in GMPs. In contrast, C/EBP was found to be indispensable in an already established leukemia. These results suggest that C/EBP play an important role in the early transforming event of leukemogenesis.
Publication Title
Initiation of MLL-rearranged AML is dependent on C/EBPα.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their physiological role in adipose tissue biology and systemic energy metabolism has not been established. Here we show that adipose tissue expression of Blnc1, a conserved lncRNA regulator of thermogenic genes, is highly induced in obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning, exacerbates obesity-associated brown fat whitening, and worsens adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health.
Publication Title
The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples