期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/ijms22083975
关键词
astrocyte; neuron; noradrenaline; transcriptomic; chromatin
资金
- National Institutes of Health, NINDS [NS071153, NS096096]
This study explores how neuronal-derived signals influence astrocyte function at the gene expression level, highlighting distinct transcriptomic and chromatin accessibility changes in response to different neuroactive compounds. Noradrenaline shows a more profound effect on astrocyte transcriptional profiles compared to other neurotransmitters, indicating potential dysregulated genetic mechanisms of astrocyte-neuron communication in neurological disorders.
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.
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