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SRP058534
Homo sapiens
10 Downloadable Samples
IlluminaHiSeq2500
Description
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.
Publication Title
ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta, Pan troglodytes, Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta, Pan troglodytes, Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We identified human-specific gene expression patterns in the brain by comparing expression with chimpanzee and rhesus macaque
Publication Title
Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity.
Publication Title
Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluritpotent cells into cells with hepatocyte characteristics. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation toward a hepatocytelike fate appeared to recapitulate many of the stages normally associated with the formation of hepatocytes in vivo. In the current study we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate i) that human ES cells express a number of mRNAs that characterize each stage in the differentiation process, ii) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses, and iii) that the nuclear hormone receptor HNF4a is essential for specification of human hepatic progenitor cells by establishing expression of the network of transcription factors that control hepatocyte cell fate.
Publication Title
HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To study the role of hepatic nuclear factor alpha (HNF4a in hepatogenesis, we used loxP-Cre technology to eliminate it from developing mouse livers.
Publication Title
Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 173 Downloadable Samples
- Illumina HiSeq 2500
Description
The synthetic cost of cycling genes is higher than other genes, and the cyclic expression pattern of these genes is a strategy for reducing the overall energy usage of cells Overall design: Samples for both conditions were taken over two metabolic cycles. For the fast cycling condition one sample was taken every 13 minutes for ~4.25 hours. For the slow cycling condition, samples were taken every 36 minutes for ~14.5 hours. Cycling genes were identified using JTK_Cycle (Hughes et al. (2010) Journal of Biological Rhythms).
Publication Title
Cycling Transcriptional Networks Optimize Energy Utilization on a Genome Scale.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 52 Downloadable Samples
- IlluminaHiSeq2000
Description
We carried out RNA-sequencing (RNA-seq) of adult human postmortem neocortical brain tissue, and then correlated those expression values with the fMRI signal in each brain region Overall design: Ten cortical regions were included in the analysis: pre-motor cortex - PMV (BA6), dorsolateral prefrontal cortex – DLPFC (BA9), middle temporal gyrus – pMTG (BA21), superior temporal gyrus – pSTG (BA22), angular gyrus - AG (BA39), supramarginal gyrus - SMG (BA40), pars opercularis - POP (BA44), pars triangularis - PTr (BA45), middle frontal gyrus – MFG (BA46) and pars orbitalis - POrB (BA47). For each brain region, three or more samples from left adult brain hemispheres were collected (ages range from 33 to 49) and only males were included to avoid the effect of sex
Publication Title
Correspondence between Resting-State Activity and Brain Gene Expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina Genome Analyzer II
Description
We used RNA sequencing to identify the RBFOX1 splicing network at a genome-wide level in primary human neural stem cells during differentiation. We observe that RBFOX1 regulates a large set of alternative splicing events implicated in neurogenesis and cell maintenance. Subsequent alterations in gene expression define an additional transcriptional network regulated by RBFOX1 involved in neurodevelopmental pathways remarkably parallel to those affected by splicing. Overall design: RNA sequencing at a 75bp single-end read scale was performed using polyA-enriched RNA from 5 biological replicates of primary human neural progenitor cell lines generated by lentiviral-mediated knockdown of GFP (control) or RBFOX1 and differentiated for 4 weeks.
Publication Title
RBFOX1 regulates both splicing and transcriptional networks in human neuronal development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
mRNA from bone marrow-derived MSCs stably expressing CTGF-specific shRNA (or empty vector control) was analyzed for differential gene expression. Significant differences were found in cell proliferation-related genes, especially genes related to the M phase of the cell cycle, which were down-regulated in CTGF-knockdown-MSCs compared to control MSCs.
Publication Title
Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment.
Sample Metadata Fields
Specimen part
View Samples