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SRP071754
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2000
Description
We profiled total liver mRNA of WT and p21KO mice that were fed ad libitum or fasted for 24 hours Overall design: 2-3 mice of each genotype were either fed or fasted for 24 hours, sacrificed and total mRNA was extracted from liver (we mapped >12M reads per sample)
Publication Title
p21<sup>Cip1</sup> plays a critical role in the physiological adaptation to fasting through activation of PPARα.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
c-Fos, a member of the stress-activated Activator Protein 1 (AP-1) transcription factor family, is expressed in human hepatocellular cancer (HCC). Using genetically engineered mouse models (GEMMs) we show that hepatocyte-specific expression of c-Fos leads to a proliferative, de-differentiated phenotype, whereas hepatocyte-specific deletion of c-Fos protects against diethylnitrosamine (DEN)-induced liver cancer. Furthermore, c-Fos-expressing livers resemble human HCCs based on expression profiles. In the present RNA seq, we intend to analyze the transcriptomic profile of livers at 2 and 4 mo hepatocyte-specific c-Fos expression compared to the corresponding age-matched control mice. Moreover, we analyzed livers of mice with hepatocyte-specific deletion c-Fos at 48h after DEN treatment compared to identically treated control mice. Overall design: The general idea was to analyze the transcriptomic profile of hepatocyte-specific c-Fos over-expressing livers at 2 and 4 mo expression. Hereby, a hepatocyte-specific doxycycline (Dox)-switchable mouse model was (LAP-tTA; col1a1:Tet-O-fosFlag) was generated and c-Fos expression was induced at the age of 3 weeks by removal of doxycycline. Each sample LaptTA-fos-MUT represents an individual hepatocyte-specific c-fos expressing mouse at the indicated time-point and the corresponding identically treated control mouse LaptTA-fos-CO. Moreover, the transcriptomic profile of livers with hepatocyte-specific deletion of c-Fos at 48h after diethylnitrosamine (DEN)-induced liver cancer initiation was analyzed. For hepatocyte-specific knock-out of c-Fos, mice with conditional alleles of c-fos and the Alfp-Cre transgene were used. Control mice only carried the Alfp-Cre transgene. At the age of 8 weeks these mice were injected with 100mg/kg DEN. Each sample AlfpCre-fos-MUT_DEN represents an individual hepatocyte-specific c-fos knock-out mouse 48h after DEN and the identically treated control mouse AlfpCre-fos-CO-Cre+_DEN.
Publication Title
Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 103 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
We have developed a total RNA amplification and labeling strategy for use with Affymetrix GeneChips. Our protocol, which we denote BIIB, employs two rounds of linear T7 amplification followed by Klenow labeling to generate a biotinylated cDNA. In benchmarking studies using a titration of mouse universal total RNA, BIIB outperformed commercially available kits in terms of sensitivity, accuracy, and amplified target length, while providing equivalent results for technical reproducibility. BIIB maintained 50 and 44% present calls from 100 and 50 pg of total RNA, respectively. Inter- and intrasample precision studies indicated that BIIB produces an unbiased and complete expression profile within a range of 5 ng to 50 pg of starting total RNA. From a panel of spiked exogenous transcripts, we established the BIIB linear detection limit to be 20 absolute copies. Additionally, we demonstrate that BIIB is sensitive enough to detect the stochastic events inherent in a highly diluted sample. Using RNA isolated from whole tissues, we further validated BIIB accuracy and precision by comparison of 224 expression ratios generated by quantitative real-time PCR. The utility of our method is ultimately illustrated by the detection of biologically expected trends in a T cell/B cell titration of 100 primary cells flow sorted from a healthy mouse spleen.
Publication Title
Accurate and precise transcriptional profiles from 50 pg of total RNA or 100 flow-sorted primary lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 54 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptional dysregulation in Huntingtons disease (HD) is an early event that affects the expression of genes involved in survival and neuronal functions throughout the progression of the pathology. In the last years, extensive research has focused on epigenetic and chromatin-modifying factors as a causative explanation for such dysregulation, offering attractive targets for pharmacological therapies. In this work we examined the gene expression profiles in cortex, striatum, hippocampus and cerebellum of juvenile R6/1 and N171-82Q mice, two models of fast progressive HD, to retrieve the early transcriptional signatures associated with this pathology.These profiles showed significant coincidences with the transcriptional changes in the conditional knockout for the lysine acetyltransferase CBP in postmitotic forebrain neurons.
Publication Title
Early alteration of epigenetic-related transcription in Huntington's disease mouse models.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Macrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear.results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b+/Ly6C+ monocyte/macrophage populations in the pathophysiology of disease after AKI.
Publication Title
Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favored development of epigenetic drugs. In this study, we have design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of hematological neoplasia (Acute Myeloid Leukemia-AML, Acute Lymphoblastic Leukemia-ALL and Diffuse Large B-cell Lymphoma-DLBCL) with the lead compound CM-272, inhibited cell proliferation and promoted apoptosis, inducing interferon stimulated genes and immunogenic cell death. CM-272 significantly prolonged survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series, as a promising therapeutic tool for unmet needs in hematological tumors.
Publication Title
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Sample Metadata Fields
Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
The Endoplasmic Reticulum–Mitochondria Encounter Structure (ERMES) is a protein complex that tethers the two organelles and creates the physical basis for communication between them. ERMES functions in lipid and calcium exchange between the ER and mitochondria, mitochondrial protein import and maintenance of mitochondrial morphology and genome. Here we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of ERMES known roles in calcium regulation, phospholipid biosynthesis or mitochondrial biology. A mutation in the vacuolar protein sorting 13 (VPS13) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our study reveals that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels. Overall design: various mutants
Publication Title
Endoplasmic reticulum-mitochondria junction is required for iron homeostasis.
Sample Metadata Fields
Subject
View Samples- Saccharomyces cerevisiae
- 11 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The N-terminal tail of histone H2A shows evolutionary changes that parallel genome size and aid chromatin compaction. As genome size increases, so does the number of arginines. In contrast, serines corellate with small genomes. Examples for such changes are arginine in position 11 and serine in position 15.
Publication Title
Evolution of histone 2A for chromatin compaction in eukaryotes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Whsc1 gene codes for a SET domain-containing H3K36 dimethylase, whose activity has been suggested, in ex vivo cell culture experiments, to control many aspects of DNA and RNA processing (replication, repair, transcription, etc). Its precise function in vivo is still unclear. Here, we use RNA-seq transcriptome analysis to study the changes in gene expression in the absence of Whsc1. Our results show that, in the experimental system used, loss of Whsc1 caused massive changes in genes affecting many fundamental cellular processes, from cell cycle to ribosome synthesis, DNA repair, replication, etc. Overall design: Whsc1-KO mice are embryonic lethal. We therefore took hematopoietic cells from fetal liver of WT and Whsc1-KO embryo littermates and injected them in to lethally irradiated RAG1-KO recipients and allowed the generation of a full Whsc1-KO hematopoietic system. Then, WT and Whsc1-KO B cells were obtained from the spleen and stimulated with LPS to induce proliferation and class switch recombination. Flow cytometry and cell cycle analyses (among others) showed the existence of serious proliferative alterations in Whsc1-KO cells. Then, we performed paired-end RNAseq analyses of 7 independent WT and 6 independent Whsc1-KO biological replicates and we used these data to identify differentially expressed genes and pathways regulated by Whsc1 in B cells.
Publication Title
Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development.
Sample Metadata Fields
Cell line, Subject
View Samples