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Project description:The communication between immune and central nervous system represents an emerging field in neuroscience with many potential consequences both in basic and translational medicine. Among the plethora of mechanisms which might be involved, it is now clear that that immune molecules released upon inflammatory state can modulate different physiological aspects of brain development, resulting in long-lasting pathological consequences which may interfere with normal behavior during adulthood. A common aspect of this immune molecule is to promote deep transcriptional changes responsible for long-term effects. Single-cell RNA sequencing is now becoming a cutting-edge technology for studying the genomic rearrangement occurring at single cell level in different experimental models, thus opening a new frontier in medicine. Here, by using primary cultured neurons as a simplified model for studying neuronal development, we study the long-term consequences of the proinflammatory cytokine interleukine-6 (IL-6) on developing neurons through a single-cell sequencing approach. Based on the immuneprofiling of the analyzed cells, we identified different neuronal and non-neuronal cell clusters whose transcriptional profile changed specifically upon the inflammatory stimulation.
2021-05-13 | GSE130803 | GEO
Project description:The communication between immune and central nervous system represents an emerging field in neuroscience with many potential consequences both in basic and translational medicine. Among the plethora of mechanisms which might be involved, it is now clear that that immune molecules released upon inflammatory state can modulate different physiological aspects of brain development, resulting in long-lasting pathological consequences which may interfere with normal behavior during adulthood. A common aspect of this immune molecule is to promote deep transcriptional changes responsible for long-term effects. Single-cell RNA sequencing is now becoming a cutting-edge technology for studying the genomic rearrangement occurring at single cell level in different experimental models, thus opening a new frontier in medicine. Here, by using primary cultured neurons as a simplified model for studying neuronal development, we study the long-term consequences of the proinflammatory cytokine interleukine-6 (IL-6) on developing neurons through a single-cell sequencing approach. Based on the immuneprofiling of the analyzed cells, we identified different neuronal and non-neuronal cell clusters whose transcriptional profile changed specifically upon the inflammatory stimulation.
2021-07-20 | GSE180344 | GEO
Project description:Single cell transcriptional profiling of cultured developing neurons upon inflammatory challenge
| PRJNA747918 | ENA
Project description:Single cell transcriptional profiling of cultured developing neurons upon inflammatory challenge [in vivo]
| PRJNA747922 | ENA
Project description:Single cell transcriptional profiling of cultured developing neurons upon inflammatory challenge [in vitro]
| PRJNA541482 | ENA
Project description:Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are characterized by intraneuronal deposition of the nuclear TAR DNA-binding protein 43 (TDP-43) caused by unknown mechanisms. Here, we studied TDP-43 in primary neurons under different stress conditions and found that only proteasome inhibition by MG-132 or lactacystin could induce significant cytoplasmic accumulation of TDP-43, a histopathological hallmark in disease. This cytoplasmic accumulation was accompanied by phosphorylation, ubiquitination and aggregation of TDP-43, recapitulating major features of disease. Proteasome inhibition produced similar effects in both hippocampal and cortical neurons, as well as in immortalized motor neurons. To determine the contribution of TDP-43 to cell death, we reduced TDP-43 expression using small interfering RNA (siRNA), and found that reduced levels of TDP-43 dose-dependently rendered neurons more vulnerable to MG-132. Taken together, our data suggests a role for the proteasome in subcellular localization of TDP-43, and possibly in disease.
| S-EPMC3146516 | biostudies-literature
Project description:BACKGROUND: During murine hypothalamic development, different neuroendocrine cell phenotypes are generated in overlapping periods; this suggests that cell-type specific developmental programs operate to achieve complete maturation. A balance between programs that include cell proliferation, cell cycle withdrawal as well as epigenetic regulation of gene expression characterizes neurogenesis. Thyrotropin releasing hormone (TRH) is a peptide that regulates energy homeostasis and autonomic responses. To better understand the molecular mechanisms underlying TRH neuron development, we performed a genome wide study of its transcriptome during fetal hypothalamic development. RESULTS: In primary cultures, TRH cells constitute 2% of the total fetal hypothalamic cell population. To purify these cells, we took advantage of the fact that the segment spanning -774 to +84 bp of the Trh gene regulatory region confers specific expression of the green fluorescent protein (GFP) in the TRH cells. Transfected TRH cells were purified by fluorescence activated cell sorting, various cell preparations pooled, and their transcriptome compared to that of GFP- hypothalamic cells. TRH cells undergoing the terminal phase of differentiation, expressed genes implicated in protein biosynthesis, intracellular signaling and transcriptional control. Among the transcription-associated transcripts, we identified the transcription factors Klf4, Klf10 and Atf3, which were previously uncharacterized within the hypothalamus. CONCLUSION: To our knowledge, this is one of the first reports identifying transcripts with a potentially important role during the development of a specific hypothalamic neuronal phenotype. This genome-scale study forms a rational foundation for identifying genes that might participate in the development and function of hypothalamic TRH neurons.
| S-EPMC3126781 | biostudies-literature
Project description:BackgroundWhile leeches in the genus Hirudo have long been models for neurobiology, the molecular underpinnings of nervous system structure and function in this group remain largely unknown. To begin to bridge this gap, we performed RNASeq on pools of identified neurons of the central nervous system (CNS): sensory T (touch), P (pressure) and N (nociception) neurons; neurosecretory Retzius cells; and ganglia from which these four cell types had been removed.ResultsBioinformatic analyses identified 3565 putative genes whose expression differed significantly among the samples. These genes clustered into 9 groups which could be associated with one or more of the identified cell types. We verified predicted expression patterns through in situ hybridization on whole CNS ganglia, and found that orthologous genes were for the most part similarly expressed in a divergent leech genus, suggesting evolutionarily conserved roles for these genes. Transcriptional profiling allowed us to identify candidate phenotype-defining genes from expanded gene families. Thus, we identified one of eight hyperpolarization-activated cyclic-nucleotide gated (HCN) channels as a candidate for mediating the prominent sag current in P neurons, and found that one of five inositol triphosphate receptors (IP3Rs), representing a sub-family of IP3Rs absent from vertebrate genomes, is expressed with high specificity in T cells. We also identified one of two piezo genes, two of ~ 65 deg/enac genes, and one of at least 16 transient receptor potential (trp) genes as prime candidates for involvement in sensory transduction in the three distinct classes of leech mechanosensory neurons.ConclusionsOur study defines distinct transcriptional profiles for four different neuronal types within the leech CNS, in addition to providing a second ganglionic transcriptome for the species. From these data we identified five gene families that may facilitate the sensory capabilities of these neurons, thus laying the basis for future work leveraging the strengths of the leech system to investigate the molecular processes underlying and linking mechanosensation, cell type specification, and behavior.
| S-EPMC7992859 | biostudies-literature
Project description:To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq) to create an atlas of the adult mouse lumbar spinal cord. We identified and molecularly characterized 43 neuronal populations. Next, we leveraged the snRNA-seq approach to provide unbiased identification of neuronal populations that were active following a sensory and a motor behavior, using a transcriptional signature of neuronal activity. This approach can be used in the future to link single nucleus gene expression data with dynamic biological responses to behavior, injury, and disease.
| S-EPMC5849084 | biostudies-literature
Project description:Transcriptome analysis based on deep expressed sequence tag (EST) sequencing allows quantitative comparisons of gene expression across multiple species. Using pyrosequencing, we generated over 7 million ESTs from four stages of developing seeds of Ricinus communis, Brassica napus, Euonymus alatus and Tropaeolum majus, which differ in their storage tissue for oil, their ability to photosynthesize and in the structure and content of their triacylglycerols (TAG). The larger number of ESTs in these 16 datasets provided reliable estimates of the expression of acyltransferases and other enzymes expressed at low levels. Analysis of EST levels from these oilseeds revealed both conserved and distinct species-specific expression patterns for genes involved in the synthesis of glycerolipids and their precursors. Independent of the species and tissue type, ESTs for core fatty acid synthesis enzymes maintained a conserved stoichiometry and a strong correlation in temporal profiles throughout seed development. However, ESTs associated with non-plastid enzymes of oil biosynthesis displayed dissimilar temporal patterns indicative of different regulation. The EST levels for several genes potentially involved in accumulation of unusual TAG structures were distinct. Comparison of expression of members from multi-gene families allowed the identification of specific isoforms with conserved function in oil biosynthesis. In all four oilseeds, ESTs for Rubisco were present, suggesting its possible role in carbon metabolism, irrespective of light availability. Together, these data provide a resource for use in comparative and functional genomics of diverse oilseeds. Expression data for more than 350 genes encoding enzymes and proteins involved in lipid metabolism are available at the 'ARALIP' website (http://aralip.plantbiology.msu.edu/).
| S-EPMC3507003 | biostudies-literature