Here, we used next-generation RNA sequencing (RNA-seq) to produce a quantitative, whole genome atlas of gene expression for every excitatory neuronal class in the hippocampus; namely, granule cells and mossy cells of the dentate gyrus, and pyramidal cells of areas CA3, CA2, and CA1. Moreover, for the canonical neurons of the trisynaptic loop, we profiled transcriptomes at both dorsal and ventral poles, producing a cell class- and region-specific transcriptional atlas for these canonical populations. Overall design: Hippocampal RNA profiles were generated by deep sequencing on Illumina HiSeq 2500, with three biological replicates per population
Hipposeq: a comprehensive RNA-seq database of gene expression in hippocampal principal neurons.
Specimen part, Subject
View SamplesTissue and organ function has been conventionally understood in terms of the interactions among discrete and homogeneous cell types. This approach has proven difficult in neuroscience due to the marked diversity across different neuron classes, but may also be further hampered by prominent within-class variability. Here, we considered a well-defined, canonical neuronal population – hippocampal CA1 pyramidal cells – and systematically examined the extent and spatial rules of transcriptional heterogeneity. Using next-generation RNA sequencing, we identified striking variability in CA1 PCs, such that the differences along the dorsal-ventral axis rivaled differences across distinct pyramidal neuron classes. This variability emerged from a spectrum of continuous expression gradients, producing a profile consistent with a multifarious continuum of cells. This work reveals an unexpected amount of variability within a canonical and narrowly defined neuronal population and suggests that continuous, within-class heterogeneity may be an important feature of neural circuits. Overall design: Hippocampal RNA profiles were generated by deep sequencing on Illumina HiSeq 2500, with three biological replicates per population
Spatial Gene-Expression Gradients Underlie Prominent Heterogeneity of CA1 Pyramidal Neurons.
Subject
View SamplesThe fragile X mental retardation protein FMRP is an RNA binding protein that regulates translation of its bound mRNAs through incompletely defined mechanisms. FMRP has been linked to the microRNA pathway and we show here that it is associated with MOV10, a putative helicase that is also associated with the microRNA pathway. We show that FMRP associates with MOV10 in an RNA-dependent manner and facilitates MOV10-association with RNAs in brain. We identified the RNA sequences recognized by MOV10 using iCLIP and found an increased number of G-quadruplexes in the CLIP sites. We provide evidence that MOV10 facilitates microRNA-mediated translation regulation and also has the novel role of increasing the expression of a subset of RNAs by sterically hindering Argonaute2 association. In summary, we have identified a new mechanism for FMRP-mediated translational regulation through its association with MOV10. Overall design: Comparison of MOV10 siRNA knockdown, irrelevant siRNA control and MOV10 overexpression on total RNA levels
MOV10 and FMRP regulate AGO2 association with microRNA recognition elements.
Specimen part, Cell line, Treatment, Subject
View SamplesThe goal was to determine how IL-12 affects gene expression by murine CTL.
IL-12 enhances CTL synapse formation and induces self-reactivity.
No sample metadata fields
View SamplesUsing the iCLIP protocol we have identified the cellular RNA entities that are bound by MOV10. We report the location and sequence of the MOV10 binding region on each RNA entity. Overall design: To identify the RNAs that bound MOV10, we UV-cross-linked HEK293F cells and immunoprecipitated with an irrelevant antibody (ir or "control") followed by a MOV10-specific antibody (MOV10) to isolate associated RNAs after stringent washing.
MOV10 and FMRP regulate AGO2 association with microRNA recognition elements.
No sample metadata fields
View SamplesWe found that the previously published Fmr1 knockout rat model of FXS expresses an Fmr1 transcript with an in-frame deletion of exon 8, which encodes for the K-homology (KH) RNA-binding domain, KH1. We observed that the deletion of exon 8 in 10 male rats within the medial prefrontal cortex (mPFC) led to transcriptional alterations compared to 12 WT rats using RNAseq. Additionally, we used weighted gene co-expression network analysis to generate 23 modules specific to the mPFC with tissue from 35 WT rat samples. Overall design: RNAseq using WT and Fmr1 delta exon 8 mPFC samples
Deletion of the KH1 Domain of Fmr1 Leads to Transcriptional Alterations and Attentional Deficits in Rats.
Age, Specimen part, Cell line, Subject
View SamplesWe used microarrays to detail genome-wide gene expression underlying cardiac myocyte pathologies and identified candidate genes and specific pathways affecting cardiac myopathies
Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation.
No sample metadata fields
View Samples