Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds

International Journal of Molecular Sciences

Junsung Woo¹  Benjamin Deneen¹  Teng-Wei Huang¹  Debosmita Sardar¹  Robert Krencik²  Caroline Cvetkovic²  ChadJ. Creighton³  Brittney Lozzi⁴ 

[1] Center for Cell and Gene Therapy, Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX 77030, USA;Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX 77030, USA;Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA;Genetics and Genomics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA;

关键词: astrocyte;    neuron;    noradrenaline;    transcriptomic;    chromatin;   

DOI  :  10.3390/ijms22083975

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown