Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPM-NM-1/M-NM-2 transcription factors and CTCF, thereby governing intricate control of neuronal development. microRNA expression profiling of maturing primary cortical neurons from E15 mouse embryos. Maturing neurons were harvested on Days 2, 4, 6 and 8.
Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPM-NM-1/M-NM-2 transcription factors and CTCF, thereby governing intricate control of neuronal development. mRNA and long non-coding RNA expression profiling of maturing primary cortical neurons from E15 mouse embryos and neurons subjected to oxygen-glucose deprivation. Maturing neurons were harvested on Days 2, 4, 6 and 8. Neurons on Day 6 were subjected to oxygen-glucose deprivation for different time periods and 24 hours reperfusion before being harvested.
Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPα/β transcription factors and CTCF, thereby governing intricate control of neuronal development.
Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPα/β transcription factors and CTCF, thereby governing intricate control of neuronal development.
Project description:The roles of long noncoding RNAs (lncRNAs) in synaptic transmission and neuronal development are emerging. Here we applied an integrated bioinformatic/biological screening strategy to identify lncRNAs that regulate synaptic vesicle release. We identified neuroLNC, a conserved neuron-specific nuclear lncRNA that modulates synaptic vesicle release, presynaptic calcium influx, neurite elongation and neuronal migration. In neurons neuroLNC interacts with a neurodegeneration-associated protein and tunes a set of presynaptic transcripts implicated in neurotransmitter release.
Project description:The evolution of brain complexity correlates with an increased expression of long, non-coding (lnc) RNAs in neuronal tissues. Although prominent examples illustrate the potential of lncRNAs to scaffold and target epigenetic regulators to chromatin loci, only few cases have been described to function during neurogenesis. We present a first functional characterization of the lncRNA LINC01322, which we term RUS for ‘RNA upstream of Slitrk3’. The RUS gene is well conserved in mammals by sequence and synteny next to the neurodevelopmental gene Slitrk3. RUS is exclusively expressed in neural cells and its expression increases along with neuronal markers during neuronal differentiation of mouse embryonic cortical neural stem cells. Depletion of RUS locks neuronal precursors in an intermediate state towards neuronal differentiation, with arrested cell cycle and increased apoptosis. RUS associates with chromatin in the vicinity of genes involved in neurogenesis, most of which change their expression upon RUS depletion. The identification of a range of epigenetic regulators as specific RUS interactors suggests that the lncRNA may mediate gene activation and repression in a highly context-dependent manner.
Project description:Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects (CHDs). Transcriptome programming during perinatal stages is important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45,167 unique transcripts were identified, including 21,916 known and 2,033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis (WGCNA) of mRNA and lncRNA datasets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while a few of them revealed chamber specific patterns. Out of 2,442 lncRNAs located within 50 KBs of protein coding genes, 11% significantly correlates with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. While this concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated CHD phenotypes lncRNA dataset: neonatal mouse heart left and right ventricles
Project description:Atrial fibrillation (AF) is currently the most prevalent arrhythmia worldwide.Recent clinical data implicate the additional contribution of non-coding RNAs in the pathogenesis of AFï¼which include microRNAs(miRNAs), endogenous small interfering RNAs, PIWIinteracting RNAs, and lncRNA. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with AF has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNA and mRNA expression profiles in myocardial sleevesof pulmonary veins between the patients who develop AF and the patients who were in normal sinus rhythm, which was performed using a second generation lncRNA microarrayï¼focusing specifically on the identification and characterization of lncRNAs and mRNA potentially involving in maintaining atrial fibrillation. We conducted an integrated analysis of myocardial sleeves of pulmonary veinsï¼PVsï¼from 12 patients (6 non-AF and 6AF) in our center, of which hypertension, diabetes, smoking and alcohol abuse were excluded, using a second generation lncRNA microarray