This SuperSeries is composed of the SubSeries listed below.
Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma.
Specimen part, Disease, Disease stage, Subject
View SamplesWe used Affymetrix HTA2.0 microarray profiling to analyze gene expression patterns in tumor and paired non-tumor tissue of HCC and CCA patients.
Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma.
Specimen part, Disease, Disease stage, Subject
View SamplesPersistent microglia activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylases JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 on a transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4, LPS and LPS+GSK-J4 challenged primary microglial (PM) and BV-2 microglial cells. Among the annotated genes, transcriptional sequencing of microglia that were treated with GSKJ4 revealed a selective effect on LPS induced gene expression in which the induction of cytokines/chemokines, interferon-stimulated genes, and prominent (transcription factors) TFs as well as previously unidentified genes that are important in inflammation was suppressed. Furthermore, we show that GSK-J4 controls important inflammatory genes targets by modulating STAT1, IRF7, and H3K27me3 level at their promoter site. These unprecedented results demonstrate the histone demethylases inhibitor GSK-J4 could have therapeutic applications for neuroinflammatory diseases. Overall design: Examination of the effects LPS on GSKJ4-treated PM microglial cells, were generated by deep sequencing on an Illumina HiSeq 2000 (101 cycles PE lane).
RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor.
Specimen part, Treatment, Subject
View SamplesUsing RNA-seq, we report that jumonji H3K27 demethylase inhibitor, GSK-J4, exerts potent anti-inflammatory effects on LPS-stimulated BV-2 microglial cells. Overall design: Examination of effects of LPS-stimulated BV2 cells with or without GSKJ4 treatment, were generated by deep sequencing on an Illumina HiSeq 2000(101 cycles PE lane).
Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia.
Specimen part, Cell line, Treatment, Subject
View SamplesUsing RNA-seq, we report here that primary microglia (PM) cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 2hrs or 4 hrs with LPS. Overall design: Examination of effects of LPS-stimulated PM microglial cells, were generated by deep sequencing on an Illumina HiSeq 2000(101 cycles PE lane).
Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia.
Specimen part, Treatment, Subject
View SamplesAnalysis of brassinosteroid (BR) and auxin effects on gene expression in Arabidopsis roots. Our genomic results indicate that BR and auxin induce largely opposite gene expression responses in primary roots. Overall design: RNA-Seq for 7-day-old Arabidopsis Col-0, dwf4, bri1-116, and bri1-116;bzr1-1D roots grown on regular medium and treated with brassinolide, auxin or mock solution for 4 hr.
Spatiotemporal brassinosteroid signaling and antagonism with auxin pattern stem cell dynamics in Arabidopsis roots.
Specimen part, Treatment, Subject
View SamplesGene expression was examined in testis and brain tissue between two species (Xenopus laevis and Xenopus borealis) and their hybrid.
Single-species microarrays and comparative transcriptomics.
Age
View SamplesScreening small molecules and drugs for activity to modulate alternative splicing, we found that amiloride, distinct from four other intracellular pH-affecting analogues, could normalize the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts in human hepatocellular carcinoma Huh-7 cells. To elucidate the underlying mechanisms, our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF and also decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, while increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulated kinases and up-regulated phosphatases in the signal pathways known to affect the splicing factor protein phosphorylation. The amiloride effects of splicing factor protein hypo-phosphorylation andnormalizedoncogenic RNA splicing were both abrogated by pre-treatment with a PP1 inhibitor. We then performed global exon array analysis of Huh-7 cells treated with amiloride for 24 hours. Using gene array chips (Affymetrix GeneChip Human Exon 1.0 ST Array of >518000 exons of 42974 genes) for exon array analysis (set parameters of correlation coefficient 0.7, splicing index -1.585 , and log2 ratio -1.585), we found that amiloride influenced the splicing patterns of 551 genes involving at least 584 exons, which included 495 known protein-coding genes involving 526 exons, many of which play key roles in functional networks of ion transport, extracellular matrix, cytoskeletons and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of abnormal RNA splicing for cancer therapeutics.
Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells.
Cell line
View SamplesUnderstanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES) cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cell (PGCs) and identified genes up-regulated in pluripotent cells both in vitro and in vivo. These genes are enriched for roles in transcription, chromatin remodeling, cell cycle and DNA repair. We developed a novel computational algorithm, CompMoby, which combines analyses of sequences both aligned and non-aligned between different genomes with a probabilistic segmentation model to systematically predict short DNA motifs that regulate gene expression. CompMoby was used to identify conserved over-represented motifs in genes up-regulated in pluripotent cells. We show that the motifs are preferentially active in undifferentiated mouse ES and Embryonic Germ cells in a sequence-specific manner, and that they can act as enhancers in the context of an endogenous promoter. Importantly, the activity of the motifs is conserved in human ES cells. We further show that the transcription factor NF-Y specifically binds to one of the motifs, is differentially expressed during ES cell differentiation and is required for ES cell proliferation. This study provides novel insights into the transcriptional regulatory networks of pluripotent cells. Our results suggest that this systematic approach can be broadly applied to understanding transcriptional networks in mammalian species.
Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.
Age, Specimen part, Time
View SamplesThis study aimed to perform transcriptome profiling of Nfic-/- and corresponding control tooth germ at root initiation stage to identify differentially expressed for key regulators of root development. Coordination between the Hertwig’s Epithelial Root Sheath (HERS) and apical papilla (AP) is crucial for proper root development process. The Hedgehog (Hh) signaling pathway and Nfic are both involved in tooth root development. Overall design: mRNA profiling of apical half of tooth germ from 6 pairs of 4-day-old Nfic-/- and littermate Nfic+/- control mice were generated using Illumina Next-Seq 500
An Nfic-hedgehog signaling cascade regulates tooth root development.
No sample metadata fields
View Samples