The subunits of voltage-gated calcium channels regulate surface expression and gating of CaV1 and CaV2 1 subunits, and thus contribute to neuronal excitability, neurotransmitter release and calcium-induced gene regulation. In addition certain subunits are targeted into the nucleus, where they directly interact with the epigenetic machinery. Whereas their involvement in this multitude of functions is reflected by a great molecular heterogeneity of isoforms derived from four genes and abundant alternative splicing, little is known about the roles of individual variants in specific neuronal functions. In the present study, an alternatively spliced 4 subunit lacking the variable N-terminus (4e) is identified. It is highly expressed in mouse cerebellum and cultured cerebellar granule cells (CGC) and modulates P/Q-type calcium currents in tsA cells and CaV2.1 surface expression in neurons. Compared to the other two known full-length 4 variants (4a, 4b) 4e is most abundantly expressed in the distal axon, but lacks nuclear targeting properties. To examine the importance of nuclear targeting of 4 subunits for transcriptional regulation, we performed whole genome expression profiling of CGCs from lethargic mice individually reconstituted with 4a, 4b, and 4e. Notably, the number of genes regulated by each 4 splice variant correlated with the rank order of their nuclear targeting properties (4b> 4a> 4e). Together these findings support isoform-specific functions of 4 splice variant in neurons, with 4b playing a dual role in channel modulation and gene regulation, while the newly detected 4e variant serves exclusively in calcium channel-dependent functions.
Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.
Specimen part
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Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination.
Disease, Disease stage
View SamplesThis study investigated the specific and differential gene expression in human immature DCs (iDCs) in response to treatment with a butanol fraction containing defined bioactive phytocompounds extracted from stems and leaves of Echinacea purpurea
Genomics and proteomics of immune modulatory effects of a butanol fraction of echinacea purpurea in human dendritic cells.
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View SamplesYAP knockdown in HUVEC elicits proliferation and cell cycle preogression defects. YAP deficient cells caused arrest in G1 and defects in S-phase entry. The microarray analysis was conducted to identify potential YAP targets that are involved in HUVEC cell cycle regulation
YAP regulates S-phase entry in endothelial cells.
Specimen part, Treatment
View SamplesWe report the transcriptome of single pancreatic cells at embryonic day e13.5 Overall design: Single cells mRNA of wild-type mouse pancreata at embryonic day 13.5
Single cell transcriptomic profiling of mouse pancreatic progenitors.
Specimen part, Cell line, Subject
View SamplesPurpose: To determine effects of arsenic on gene expression in polarized primary human bronchial epithelial (HBE) cells and impact on transcriptional response to Pseudomonas aeruginosa infection Methods: mRNA profiles of HBE cells from 6 donors exposed to 0, 5, 10 or 50 ug/L total arsenic +/- Pseudomonas aeruginosa (48 samples) were generated using Illumina sequencing, aligned in CLC Genomics workbench and analyzed for DE in EdgeR Findings: 20-30 million reads were mapped per sample and transcripts were identifed that were significantly differentially expressed in response to arsenic and Pseudomonas aeruginosa Overall design: Gene expression profiles of HBE cells from 6 donors exposed to three concentrations of arsenic +/- Pseudomonas were generated using mRNA sequencing
Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Coassembly of REST and its cofactors at sites of gene repression in embryonic stem cells.
Cell line, Treatment
View SamplesAnalysis of gene expression profiling upon REST shRNA knockdown in mouse ES cells for 72 hours,
Coassembly of REST and its cofactors at sites of gene repression in embryonic stem cells.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The long noncoding RNA RMST interacts with SOX2 to regulate neurogenesis.
Cell line, Treatment
View SamplesFollicle assembly is the process by which groups or nests of oocytes break down to form primordial follicles. The size of the primordial follicle pool is the major determinant of the reproductive lifespan of a female. Previously, progesterone (P4) has been shown to inhibit follicle assembly, while tumor necrosis factor alpha (TNF-alpha) has been shown to promote the apoptosis that is necessary for follicle assembly. The current study examines how TNF-alpha and progesterone interact to regulate primordial follicle assembly. Ovaries were collected from newborn rats and placed in organ culture to examine the actions of P4 and TNF-alpha. P4 was found to decrease primordial follicle assembly and increase the percentage of un-assembled oocytes both in vitro and in vivo. TNF-alpha treatment did not change the proportion of assembled follicles in cultured ovaries, but did block the ability of P4 to inhibit follicle assembly. Microarray analysis of the ovarian transcriptome revealed that progesterone treatment of the ovaries altered the expression of 513 genes with 132 only expressed after P4 treatment and 16 only expressed in control ovaries. The majority of genes were up-regulated greater than 2-fold over control, with a small subset of 16 genes down-regulated. Categories of genes affected by P4 are described including a group of extra-cellular signaling factors. The progesterone receptors expressed at the time of follicle assembly included the surface membrane progesterone receptors PGRMC1, PGRMC2 and RDA288. The nuclear genomic P4 receptor was not expressed at appreciable levels. Progesterone increased the expression of several genes (TANK, NFkappaB, Bcl2l1 and Bcl2l2) involved in a signaling pathway that promotes cell survival and inhibits apoptosis. Observations indicate that P4 acts through the surface membrane progesterone receptors to regulate primordial follicle assembly, and that TNF-alpha can over-ride the inhibitory actions of P4 on follicle assembly. A major mechanism involved in the actions of P4 is an increase in cell survival genes and inhibition of the apoptosis pathway. Observations provide insight into the hormonal regulation of primordial follicle assembly and lead to novel approaches to potentially manipulate follicle assembly and reproductive capacity.
Interactions between progesterone and tumor necrosis factor-alpha in the regulation of primordial follicle assembly.
No sample metadata fields
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