Idiopathic portal hypertension (IPH) is characterized by portal hypertension due to obstruction or stenosis of the intrahepatic peripheral portal branches. Researchers have suggested that IPH may be attributed to intrahepatic peripheral portal vein thrombosis, splenic factors, abnormal autoimmunity, and related factors, however, the etiology of IPH remains unclear.
Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension.
Specimen part, Disease stage
View SamplesSphingomyelin synthase (SMS) 2 is the synthetic enzyme of sphingomyelin (SM), which regulates the fluidity and microdomain structure of the plasma membrane. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis, and found suppression of DSS-induced inflammation in SMS2 deficient (SMS2-/-) mice. Results provide insight into the role of SMS2 in inflammation.
Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer.
Specimen part, Treatment
View SamplesDiffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor, resulting in the death of 200-300 children each year in the United States. Recently it was discovered that approximately 25% of all DIPG cases harbor activating mutations in ACVR1, a gene that encodes Activin A receptor (ALK2), a receptor in the bone morphogenetic protein (BMP) pathway, and that DIPGs with ALK2 mutations commonly harbor an H3.1K27M mutation. Herein, we used the RCAS/TVA retroviral system to study the effects of ACVR1 mutations and H3.1K27M on DIPG pathogenesis. In vitro expression of R206H ACVR1 with and without H3.1K27M in nestin-expressing brainstem progenitors resulted in upregulation of mesenchymal markers and gene set enrichment analysis (GSEA) revealed Stat3 pathway activation. Neonatal expression of ACVR1 R206H or G328V in combination with H3.1K27M and p53 deletion in nestin-expressing brainstem progenitors induced glioma-like lesions expressing mesenchymal markers with Stat3 activation but was not sufficient for full gliomagenesis. In combination with platelet-derived growth factor A (PDGFA) signaling, ACVR1 R206H and H3.1K27M significantly decreased survival and increased tumor incidence. We demonstrate that targeting the BMP signaling pathway may be an effective therapeutic strategy to treat ACVR1 R206H mutant DIPGs. Exogenous Noggin expression at tumor initiation significantly increased tumor latency and treatment of ACVR1 R206H mutant murine DIPGs with LDN212854, an ACVR1 inhibitor, significantly prolonged their survival. We confirm relevance of our model to the human disease as human DIPG models with ACVR1 mutations were also sensitive to treatment with LDN212854 in vitro. Altogether, our studies demonstrate that ACVR1 R206H and H3.1K27M promote tumor initiation, accelerate gliomagenesis, promote a mesenchymal profile in part due to Stat3 activation, and identify LDN212854 as a promising compound to treat children with DIPG. Overall design: We use RNAseq to study the transcriptomal effects of ACVR1 WT or R206H ACVR1 mutation alone and in combination with H3.1K27M mutation on murine nestin-expressing brainstem progenitors at P3-5 (using RCAS/TVA). Key findings were validated by Real-Time PCR.
ACVR1 R206H cooperates with H3.1K27M in promoting diffuse intrinsic pontine glioma pathogenesis.
Specimen part, Subject
View SamplesMedulloblastoma is the most common pediatric CNS cancer. In order to identify important molecules important for deregulated tumor cell growth, we use microarray to detail the global gene expression profile in Shh-driven mouse medulloblastomas and determine the most differentially expressed genes compared to the control wild-type cerebellum.
Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics.
Age, Specimen part
View SamplesCharacterizing the impact of pharmacological and shRNA-mediated silencing of EAG2 in medulloblastoma.
EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.
Specimen part, Cell line
View SamplesA dataset for coordinated transcriptome analysis of the effect of ethanol on human embryonic cerebral slices in vitro and on the mouse embryonic cerebral cortex in a in vivo model.
Combined transcriptome analysis of fetal human and mouse cerebral cortex exposed to alcohol.
Time
View SamplesAs Trypanosoma cruzi, the etiological agent of Chagas disease, multiplies in the cytoplasm of nucleated host cells, infection with this parasite is highly likely to affect host cells. We performed an exhaustive transcriptome analysis of T. cruzi-infected HeLa cells using an oligonucleotide microarray containing probes for greater than 47,000 human gene transcripts. In comparison with uninfected cells, those infected with T. cruzi showed greater than threefold up-regulation of 41 genes and greater than threefold down-regulation of 23 genes. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of selected, differentially expressed genes confirmed the microarray data. Many of these up- and down-regulated genes were related to cellular proliferation, including seven up-regulated genes encoding proliferation inhibitors and three down-regulated genes encoding proliferation promoters, strongly suggesting that T. cruzi infection inhibits host cell proliferation, which may allow more time for T. cruzi to replicate and produce its intracellular nests. These findings provide new insight into the molecular mechanisms by which intracellular T. cruzi infection influences the host cell, leading to pathogenicity.
Transcriptome profile of Trypanosoma cruzi-infected cells: simultaneous up- and down-regulation of proliferation inhibitors and promoters.
No sample metadata fields
View SamplesIdentfification of MEF2A target genes using ChIP-exo and RNA-seq in skeletal muscle and primary cardiomyocytes. MEF2 plays a profound role in the regulation of transcription in cardiac and skeletal muscle lineages. To define the overlapping and unique MEF2A genomic targets, we utilized ChIP-exo analysis of cardiomyocytes and skeletal myoblasts. Of the 2783 and 1648 MEF2A binding peaks in skeletal myoblasts and cardiomyocytes, respectively, 294 common binding sites were identified. Genomic targets were compared to differentially expressed genes in RNA-seq analysis of MEF2A depleted myogenic cells. Overall design: The effect of MEF2A gene silencing on gene expression in myoblasts was assessed at 48 hr DM. Up and downregulated genes were then compared to MEF2A target genes identified in ChIP-exo analysis of 48 hr DM C2C12 myoblasts cells and primary cardiomyocytes.
Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling.
No sample metadata fields
View SamplesThe concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years. Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions. Overall design: Two temporal assays of Caenorhabditis elegans embryonic development, starting at the zygote: (a) Embryos collected at fixed (~10 minute) time intervals. (b) Embryo segregates, up to five lines of blastomeres, isolated in reference to mitotic events. There were 184 samples in total, representing 100 distinct data points (50 in each assay).
Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer.
Subject, Time
View SamplesDuring cerebellar development, the main portion of the cerebellar plate neuroepithelium (NE) gives birth to Purkinje cells and interneurons, while the germinal zone at its dorsal edge, called the rhombic lip (RL), generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components work together to generate the intricate structure of the cerebellar anlage. In this study, we found that a polarized cerebellar anlage structure self-organizes in three-dimensional (3D) human ES cell (hESC) culture. This NE is capable of differentiating into electrophysiologically functional Purkinje cells. The addition of FGF19 promotes spontaneous generation of dorsoventrally polarized NE structures containing cerebellar and basal plates. Furthermore, further addition of SDF1 promoted the generation of stratified cerebellar plate NE with RL-like germinal zones self-forming at the edge. Thus, hESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellar anlage at the first trimester. Overall design: Examination of mRNA profile in two different treated human ES cells .
Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.
No sample metadata fields
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