The role of post-transcriptional gene regulation in human brain development and cognitive diseases remains mostly uncharacterized. ELAV-like RNA binding proteins are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission. Here, we identify the downstream transcriptional networks of ELAVL2, an RNA-binding protein with unknown function in the brain. We knockdown expression of ELAVL2 in human neurons and conduct RNA-sequencing, identifying networks of differentially expressed and alternatively spliced genes with altered ELAVL2. These networks contain autism-relevant genes as well as previously identified targets of other RNA binding proteins implicated in autism spectrum disorders such as RBFOX1 and FMRP. ELAVL2-regulated coexpression networks are also enriched for synaptic genes as well as genes with human-specific patterns of gene expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal functions at risk in autism spectrum disorders and such mechanisms of post-transcriptional gene regulation may have contributed to human brain evolution. Overall design: We carried out RNA-sequencing (RNA-seq) of human neural progenitors cells. For the RNA-seq, 5 indipendent replicates were used for the neural progenitor cells. Primary human neural progenitor cultures were derived from mid-gestation fetal brain. Cells were transduced with a lentivirus containing a specific shRNA to ELAVL2 or a control shRNA. Cells were differentiated into neurons for 4 weeks and then harvested.
ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism.
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View SamplesThe discreteness of cell fates is an inherent and fundamental feature of multicellular organisms. Here we show that cross-antagonistic mechanisms of actions of MyoD and PPARg, which are the master regulators of muscle and adipose differentiation, respectively, confer the robustness to the integrity of cell differentiation. Simultaneous expression of MyoD and PPARg in mesenchymal stem/stromal cells led to the generation of a mixture of multinucleated myotubes and lipid-filled adipocytes. Interestingly, hybrid cells, i.e., lipid-filled myotubes, were not generated, suggesting that these differentiation programs are mutually exclusive. Mechanistically, while exogenously expressed MyoD was rapidly degraded in adipocytes through ubiquitin-proteasome pathways, exogenously expressed PPARg was not down-regulated in myotubes. In PPARg-expressing myotubes, PPARg-dependent histone hyperacetylation was inhibited in a subset of adipogenic gene loci, including that of C/EBPa, an essential effector of PPARg. Thus, the cross-repressive interactions between MyoD- and PPARg-induced differentiation programs ensure the discrete cell fate decisions.
Antagonism between the master regulators of differentiation ensures the discreteness and robustness of cell fates.
Cell line, Treatment
View SamplesPaper abstract: The transcription factors Abrupt (Ab) and Knot (Kn) act as selectors of distinct dendritic arbor morphologies in two classes of Drosophila sensory neurons, termed class I and class IV, respectively. We performed binding-site mapping and transcriptional profiling of isolated these neurons. Their profiles were similarly enriched in cell-type-specific enhancers of genes implicated in neural development. We identified a total of 429 target genes, of which 56 were common to Ab and Kn; these targets included genes necessary to shape dendritic arbors in either or both of the two sensory subtypes. Furthermore, a common target gene, encoding the cell adhesion molecule Ten-m, was expressed more strongly in class I than IV, and this differential was critical to the class-selective directional control of dendritic branch sprouting or extension. Our analyses illustrate how differentiating neurons employ distinct and shared repertoires of gene expression to produce class-selective morphological traits.
Sensory-neuron subtype-specific transcriptional programs controlling dendrite morphogenesis: genome-wide analysis of Abrupt and Knot/Collier.
Specimen part
View SamplesTo more closely reproduce key cellular and stromal features of the desmoplastic reaction of cholangiocarcinoma in vitro, we developed a novel 3-dimensional culture modeling of cancer and stromal cells as a strategy for targeted therapies
Transforming Growth Factors α and β Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model.
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View SamplesBackgroundAcute coronary syndrome (ACS) is sometimes accompanied by accelerated coagulability, lipid metabolism, and inflammatory responses, which are not attributable to the cardiac events alone. We hypothesized that the liver plays a pivotal role in the pathophysiology of ACS. We simultaneously analyzed the gene expression profiles of the liver and heart during acute myocardial ischemia in mice.
Altered hepatic gene expression profiles associated with myocardial ischemia.
Sex, Specimen part
View SamplesMuscle atrophy F-box (MAFbx) is an E3 ubiquitin ligase which plays a critical role in mediating skeletal muscle atrophy. We investigated the effect of MAFbx KO in cardiac hypertrophy in response to pressure overload. A DNA microarray analysis was conducted using total RNA prepared from wild type and MAFbx KO mouse hearts subject to transverse aortic constriction (TAC). Results provide insight into the molecular mechanism to mediate the effect of MAFbx upon pathological hypertrophy.
Endogenous muscle atrophy F-box mediates pressure overload-induced cardiac hypertrophy through regulation of nuclear factor-kappaB.
Specimen part
View SamplesTranscriptome analysis of the effect of RECTAS on fibroblast cells derived from a familial dysautonomia patient.
Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice.
Sex, Age, Specimen part
View SamplesWe compared the gene expressions of the intestine, liver and spleen tissues between mice at 4 months of age and mice at 28 months of age. We used microarrays to examine the age-related changes of gene expressions of the jejunum, ileum, distal colon, liver and spleen in mice. Abbreviations used: C, 28-month-old mice; Y, 4-month-old mice.
Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice.
Sex, Age, Specimen part
View SamplesWe performed the long-term administration experiment using a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 (LB81 yogurt) for 20 months in order to understand the effects of the long-term intake of probiotics on mice. Microarrays were used to compare the gene expressions of the intestine, liver and spleen tissues between control mice and LB81 yogurt-intake mice at 28 months of age.
Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice.
Sex, Age, Specimen part
View Samples