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Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE171595 | GEO | 2021/04/07

REPOSITORIES: GEO

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Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds.

Project description:Astrocytes play central roles in normal brain function and are critical components of synaptic networks that oversee behavioral outputs. Despite their close affiliation with neurons, how neuronal-derived signals influence astrocyte function at the gene expression level remains poorly characterized, largely due to difficulties associated with dissecting neuron- versus astrocyte-specific effects. Here, we use an in vitro system of stem cell-derived astrocytes to identify gene expression profiles in astrocytes that are influenced by neurons and regulate astrocyte development. Furthermore, we show that neurotransmitters and neuromodulators induce distinct transcriptomic and chromatin accessibility changes in astrocytes that are unique to each of these neuroactive compounds. These findings are highlighted by the observation that noradrenaline has a more profound effect on transcriptional profiles of astrocytes compared to glutamate, gamma-aminobutyric acid (GABA), acetylcholine, and serotonin. This is demonstrated through enhanced noradrenaline-induced transcriptomic and chromatin accessibility changes in vitro and through enhanced calcium signaling in vivo. Taken together, our study reveals distinct transcriptomic and chromatin architecture signatures in astrocytes in response to neuronal-derived neuroactive compounds. Since astrocyte function is affected in all neurological disorders, this study provides a new entry point for exploring genetic mechanisms of astrocyte-neuron communication that may be dysregulated in disease.

| S-EPMC8069033 | biostudies-literature

Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds

Project description:Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds

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Profiling astrocyte transcriptional signatures in response to neurons and neuroactive compounds [RNA-seq]

Project description:The goal of the study is to profile molecular signature of astrocytes in response to neuronal contact and neuroactive chemicals. We performed RNA-seq on (1) mouse embryonic stem cell derived astrocytes (mES_astrocytes) from different time points of culture to determine transcriptomic changes as astrocytes mature over time in culture, (2) mES_astrocytes cocultured with human neurons to determine how neurons affect astrocyte gene expression and (3) mES_astrocytes cultured in presence of neuroactive chemicals (glutamate, gamma-aminobutyric acid, acetylcholine, noradrenaline, and serotonin) to determine transcriptomic changes induced by different types of neuronal signaling.

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Profiling astrocyte transcriptional signatures in response to neurons and neuroactive compounds [RNA-seq]

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