Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA362458 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5185500_1.fastq.gz | Fastqsanger.gz | |||
| SRR5185500_2.fastq.gz | Fastqsanger.gz | |||
| SRR5185510_1.fastq.gz | Fastqsanger.gz | |||
| SRR5185510_2.fastq.gz | Fastqsanger.gz | |||
| SRR5185520_1.fastq.gz | Fastqsanger.gz |
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Project description:Single cell RNAseq characterization of cell types produced over time in an in vitro model of human inhibitory interneuron differentiation.
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Project description:Characterization of cell types produced over time in an in vitro model of human inhibitory interneuron differentiation.
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Project description:Diverse cell types are produced from dorsal and ventral regions of the developing neural tube. In this study we describe a system for generating human inhibitory interneurons by ventralizing human embryonic stem cells in vitro and characterizing the gene expression of the cell types produced over time. We engineered a DCX-Citrine/Y hESC line to sort and characterize progenitor and neuron transcriptomics separately at both the subpopulation and single cell level. The cells generated in vitro were compared to similar populations present in human fetal brain samples by mapping gene expression data from human fetal cells onto the principal component analysis (PCA) space of in vitro-derived populations. Weighted gene co-expression network analysis (WGCNA) was used to determine the discreet cell types present at D24, D54, D100 and D125 of culture, and describe the gene expression changes that occur in progenitor and neuron populations over time. Immature lateral ganglionic eminence and medial ganglionic eminence cells are present at early timepoints, along with MGE-like and dorsal pallium-like neuronal progenitors. At later timepoints we observe the emergence of SST-expressing interneurons, as well as oligodendrocyte and astrocyte progenitors. We also identified genes that were upregulated in somatostatin-expressing interneurons as they mature.
2017-03-10 | GSE93593 | GEO
Project description:Diverse cell types are produced from dorsal and ventral regions of the developing neural tube. In this study we describe a system for generating human inhibitory interneurons by ventralizing human embryonic stem cells in vitro and characterizing the gene expression of the cell types produced over time. We engineered a DCX-Citrine/Y hESC line to sort and characterize progenitor and neuron transcriptomics separately at both the subpopulation and single cell level. The cells generated in vitro were compared to similar populations present in human fetal brain samples by mapping gene expression data from human fetal cells onto the principal component analysis (PCA) space of in vitro-derived populations. Weighted gene co-expression network analysis (WGCNA) was used to determine the discreet cell types present at D24, D54, D100 and D125 of culture, and describe the gene expression changes that occur in progenitor and neuron populations over time. Immature lateral ganglionic eminence and medial ganglionic eminence cells are present at early timepoints, along with MGE-like and dorsal pallium-like neuronal progenitors. At later timepoints we observe the emergence of SST-expressing interneurons, as well as oligodendrocyte and astrocyte progenitors. We also identified genes that were upregulated in somatostatin-expressing interneurons as they mature.
2017-03-10 | GSE93801 | GEO
Project description:We analysed scRNA-seq data in human pluripotent stem cell-derived medial ganglionic eminence (MGE) organoids. This in vitro system recapitulates some key aspects of humam MGE development including inhibitory cortical interneuron diversification.
2025-07-03 | GSE301434 | GEO
Project description:The mammalian cerebral cortex comprises a complex neuronal network that maintains a delicate balance between excitatory neurons and inhibitory interneurons. Previous studies, including our own research, have shown that specific interneuron subtypes are closely associated with particular pyramidal neuron types, forming stereotyped local inhibitory microcircuits. However, the developmental processes that establish these precise networks are not well understood. Here we show that pyramidal neuron types are instrumental in maintaining the terminal differentiation and survival of specific associated interneuron subtypes. In a wild-type cortex, the relative abundance of different interneuron subtypes aligns precisely with the pyramidal neuron types with which they synaptically target. In Fezf2 mutant cortex, characterized by the absence of layer 5 pyramidal tract neurons and an expansion of layer 6 intratelencephalic neurons, we observed a corresponding decrease in associated layer 5b interneurons and an increase in layer 6 subtypes. Interestingly, these shifts in composition are achieved through mechanisms that are specific to different interneuron types. While SST interneurons adjust their abundance to the change in pyramidal neuron prevalence through the regulation of programmed cell death, parvalbumin cells alter their identity. These findings illustrate two key strategies by which the dynamic interplay between pyramidal neurons and interneurons allows local microcircuits to be sculpted precisely. These insights underscored the precise roles of extrinsic signals from pyramidal cells in the establishment of interneuron diversity and their subsequent integration into local cortical microcircuits.
2024-08-15 | GSE272706 | GEO
Project description:<p>GABAergic interneurons are essential for neural circuit function and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and ultimately therapeutic cell replacement. We used a protocol for generating cortical interneurons from hESCs and analyzed the properties and maturation timecourse of cell types using single-cell RNAseq (data available at <a href="https://www.ncbi.nlm.nih.gov/geo/">GEO</a> under: GSE93802 on March 10 2017). Transcriptomic profiles of the hESC-derived interneurons were compared to several different populations of cells from mid-gestation human neocortex that showed differing levels of <a href="https://www.ncbi.nlm.nih.gov/gene/5080">PAX6</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/6657">SOX2</a> expression.</p> <p>For this study, 104 samples of 100 human neocortical cells each, have been sorted based on <a href="https://www.ncbi.nlm.nih.gov/gene/6657">SOX2</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/5080">PAX6</a> expression, mRNA recovered from the fixed cells by FRISCR, and transcriptomic profiles generated by SmartSeq2. The RNA-seq data from the 104 100-cell samples is included in this dbGaP study.</p>
| phs001276 | dbGaP
Project description:Gene regulatory elements such as enhancers dynamically regulate gene expression in a tissue-specific manner. However, the transcriptional regulatory elements during human inhibitory interneuron differentiation and their role in neurodevelopmental disorders are unknown. Here, we generate gene regulatory element maps of human inhibitory-like interneurons derived from embryonic stem cells (H9-ESC), permitting large-scale annotation of previously uncharacterized regulatory elements relevant to inhibitory interneuron differentiation. Our analyses identify neuronal progenitor enhancers that likely regulate the expression of transcription factors that are essential for interneuron differentiation. Focusing on dynamic changes in chromatin organization, FOXG1 and ZEB2, where the chromatin organization is changed in interneuron progenitors compared to different stages during the differentiation. Using 4C-seq and an in vivo enhancer assay, we characterized neuronal enhancers at the FOXG1 locus that interact with the FOXG1 promoter region and showed activity patterns that resemble FOXG1 expression. Using CRISPR/Cas9 genome editing, we deleted FOXG1 enhancer/s that reduced FOXG1 expression in glioblastoma cells and altered cell proliferation. Furthermore, a microdeletion proximal to FOXG1 encompassing these neuronal FOXG1 enhancers was found in a patient with Rett-like syndrome, supporting the role of FOXG1 enhancers in this syndrome. Thus, our study elucidates the gene regulatory networks of human inhibitory interneurons. Furthermore, it provides a framework for understanding the impact of non-coding regulatory elements during inhibitory interneuron differentiation, and highlights novel mechanisms underlying neurodevelopmental disorders.
2023-03-15 | GSE218668 | GEO
Project description:Synapses are fundamental organizers of precise signal propagation between neurons. Maintaining synapse assemblies require interactions between pre- and post- synaptic proteins, notably cell adhesion molecules (CAMs). It has been proposed that the function of Neuroligins (Nlgn1 - 4), postsynaptic CAMs, relies on the formation of trans-synaptic complexes with Neurexins (Nrxs), presynaptic CAMs. Nlgn3 is a unique Nlgn isoform that localizes at both excitatory and inhibitory synapses. However, Nlgn3 function mediated through Nrx interaction is mostly unknown. Here, we find for the first time that Nlgn3 localizes at postsynaptic sites apposing vesicular glutamate transporter 3 (VGT3)-expressing inhibitory terminals. Overexpression and knockdown approaches indicate that Nlgn3 regulates VGT3-positive inhibitory interneuron-mediated synaptic transmission. Fluorescent in situ hybridization and single-cell RNA sequencing studies revealed that αNrxn1 and βNrxn3 are VGT3 interneuron-specific Nrxn isoforms and the expression levels of Nrxn splice isoforms are highly diverse in VGT3 interneurons, respectively. Most importantly, postsynaptic Nlgn3 requires presynaptic αNrx1+AS4 expressed in VGT3-positive interneurons to regulate inhibitory synaptic transmission. Our results strongly suggest that specific Nlgn-Nrx interaction generate distinct functional properties at synapses.
2021-01-04 | GSE150989 | GEO
Project description:We applied massively parallel single-cell RNA-seq to profile a developmental time course of interneuron development, measuring the transcriptomes of over 60,000 progenitors during their maturation in the ganglionic eminences and embryonic migration into the cortex.
2018-03-05 | GSE104158 | GEO