Argonaute (Ago) proteins, which act in post-transcriptional gene regulation directed by small RNAs, are vital for normal stem cell biology. Here we report the genomic characterization of stable Ago-deficient mouse embryonic stem cells (mESC) and determine the direct, primary and system level response to loss of Ago-mediated regulation. We find mESCs lacking all four Ago proteins are viable, do not repress microRNA (miRNA)-targeted cellular RNAs, and show distinctive gene network signatures. Profiling of RNA expression and epigenetic activity in an Ago mutant genetic series indicates that early responses to Ago loss are driven by transcriptional regulatory networks, in particular the Tgf-ß/Smad transcriptional network. This finding is confirmed using a time course analysis of Ago depletion and Ago rescue experiments. Detailed analysis places Tgf-ß/Smad activation upstream of cell cycle regulator activation, such as Cdkn1a, and repression of the c-Myc transcriptional network. The Tgf-ß/Smad pathway is directly controlled by multiple low-affinity miRNA interactions with Tgf-ß/Activin receptor mRNAs and receptor-mediated activation is required for Tgf-ß/Smad target induction with Ago loss. Our characterization reveals the interplay of post-transcriptional regulatory pathways with transcriptional networks in maintaining cell state and likely coordinating cell state transitions. Overall design: mRNA seq from stable genetic Dicer and Dgcr8 mutant mouse embryonic stem cells.
Temporal Control of the TGF-β Signaling Network by Mouse ESC MicroRNA Targets of Different Affinities.
Specimen part, Cell line, Subject
View SamplesWe identified that downregulation of RNF20/H2Bub1 is involved in HGSOC progression through altering key immune signaling pathways. The goal of this RNA-seq is to analyze gene expression profile in FTSEC cells (FT190 and FT194 cell lines) with RNF20 knockdown (shRNF20) or control shRNA. Integrating the data from ATAC-seq for same samples, we observed that expression of immune signaling pathways have significantly changed by RNF20/H2Bub1 downregulation. Overall design: mRNA profiles of FT190 and FT194 shRNF20 (RNF20 knockdown) or control shRNA cells were generated by deep sequencing using Illumina HiSeq 2500, in triplicate.
Early Loss of Histone H2B Monoubiquitylation Alters Chromatin Accessibility and Activates Key Immune Pathways That Facilitate Progression of Ovarian Cancer.
Subject
View SamplesDifferential gene expression as a consequence of PTCD1 loss Overall design: We used RNA from control and PTCD1 knockout mice to investigate changes at the RNA level in response to PTCD1 loss
PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly.
Specimen part, Subject
View Samplesgamma delta intraepithelial lymphocytes were isolated from the colons of DSS-treated and untreated mice. Total RNAs were isolated and compared by Affymetrix DNA microarray.
Reciprocal interactions between commensal bacteria and gamma delta intraepithelial lymphocytes during mucosal injury.
No sample metadata fields
View SamplesStudies in mice have shown that PPAR is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR in human liver. Here we set out to compare the function of PPAR in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR regulates a mostly divergent set of genes in mouse and human hepatocytes.
Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
Sex, Age, Specimen part, Subject, Time
View SamplesGenomic analysis of axon pruning in Drosophila mushroom body neurons identifies the RNA-binding protein Boule as a negative regulator
Genomic analysis of Drosophila neuronal remodeling: a role for the RNA-binding protein Boule as a negative regulator of axon pruning.
Age
View SamplesStudies in mice have shown that PPAR is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR in human liver. Here we set out to compare the function of PPAR in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR regulates a mostly divergent set of genes in mouse and human hepatocytes.
Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
Sex, Age, Specimen part, Subject, Time
View SamplesStudies in mice have shown that PPAR is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR in human liver. Here we set out to compare the function of PPAR in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR regulates a mostly divergent set of genes in mouse and human hepatocytes.
Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
Sex, Age, Specimen part, Time
View SamplesSmall RNA libraries from total RNA isolated from adult ovaries Overall design: Small RNA libraries were derived from Ovaries of the Founder strain and their offspring and their reciprocal offspring. RNA from 5 individual ovaries was pooled .
piRNA dynamics in divergent zebrafish strains reveal long-lasting maternal influence on zygotic piRNA profiles.
No sample metadata fields
View SamplesDrosophila mushroom body (MB) neurons undergo axon pruning during metamorphosis through a process of localized degeneration of specific axon branches. Developmental axon degeneration is initiated at the onset of metamorphosis by the pre-pupal rise in the steroid hormone ecdysone. This study identifies genes that alter their expression in MB neurons at the onset and early steps of axon pruning.
Genomic analysis of Drosophila neuronal remodeling: a role for the RNA-binding protein Boule as a negative regulator of axon pruning.
Age
View Samples