Project description:The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) of cortical neurons derived from human embryonic stem cells (H9) treated with compounds that are inducing senescence
Project description:This experiment comprises RNA-seq data used to study evolutionary differences between humans and mice in neuronal activity-dependent transcriptional responses. Activity-dependent transcriptional responses in developing human stem cell-derived cortical neurons were compared with those induced in developing primary- or stem cell-derived mouse cortical neurons 4 hours after KCl-induced membrane depolarisation. Activity-dependent transcriptional responses were also measured in aneuploid mouse neurons carrying human chromosome 21, allowing study of the regulation of Hsa21 genes, plus their mouse orthologs, side-by-side in the same cellular environment of a mouse primary neuron.
Project description:This SuperSeries is composed of the following subset Series: GSE24440: Sprouting transcriptome in cortical neurons: young GSE24441: Sprouting transcriptome in cortical neurons: aged Refer to individual Series
Project description:Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.
Project description:Recently, direct reprogramming between divergent lineages has been achieved by introducing cell-fate-determining transcription factors. This progress may provide alternative cell resources for drug discovery and regenerative medicine. However, the genetic manipulation may limit the future application of these approaches. In this study, we identified a novel small-molecule cocktail that directly converted fibroblasts into neuronal cell fate with a high yield up after 16-days of induction. After a further maturation stage, these chemically-induced neurons (CiNs) possessed neuron-specific expression patterns, generated action potentials and formed functional synapses. Gene expression profiling revealed the activation of neuronal specific genes in the early stage of small molecule treatment. Overall, our findings prove the principle of chemically-induced direct reprogramming of somatic cell fates across germ layers without genetic manipulation, and show that cell fate can be manipulated through disrupting initial cell program and activating target cell master genes with pure chemicals. Total of 15 samples were analyzed, including mouse fibroblasts, mouse cortical primary neurons and chemically-induced neurons by different duration of chemical induction (Day0, Day4, Day8, Day19) and different small-molecule cocktail (FICB, FICB-1)
Project description:Chemical inhibition of histone demethyase LSD1 and histone methyltransferase DOT1L promotes maturation of neurons derived from pluripotent stem cells. We profiled the genome distribution of histone marks targeted by these enzymes in immature hPSC-derived cortical neurons.
Project description:E18 embryonic rat cortical neurons cultured in vitro are infected with lentivirus expressing control or PHF6shRNA-2, and harvested 5 days after infection pLL3.7 lentivirus expressing control or PHF6shRNA-2 was generated in 293T cells and concentrated using ultracentrifuge. In vitro cultured cortical neurons were infected and RNA was harvested 5 days after infection. PHF6 knockdown was validated by QPCR before sample was processed for microarray analysis.
Project description:Glutamate is a major excitatory neurotransmitter in the nervous system. Increased and persistent release of glutamate is toxic to neurons and this excitotoxicity is a hallmark of several neurodegenerative diseases. Here, we use GRO-seq to screen for the acute transcriptional changes induced by glutamate exposure on embryonic mouse cortical neurons to reveal downstream molecules which could participate in glutamate-induced toxicity. We show that several miRNA genes, such as miR-21, have altered expression upon glutamate exposure.