Multiomic integration reveals neuronal-extracellular vesicle coordination of gliotic responses in degeneration
Details
Publication Year 2023-12,Volume 12,Issue #12,Page e12393
Journal Title
Journal of Extracellular Vesicles
Publication Type
Research article
Abstract
In the central nervous system (CNS), including in the retina, neuronal-to-glial communication is critical for maintaining tissue homeostasis including signal transmission, transfer of trophic factors, and in the modulation of inflammation. Extracellular vesicle (EV)-mediated transport of molecular messages to regulate these processes has been suggested as a mechanism by which bidirectional communication between neuronal and glial cells can occur. In this work we employed multiomics integration to investigate the role of EV communication pathways from neurons to glial cells within the CNS, using the mouse retina as a readily accessible representative CNS tissue. Further, using a well-established model of degeneration, we aimed to uncover how dysregulation of homeostatic messaging between neurons and glia via EV can result in retinal and neurodegenerative diseases. EV proteomics, glia microRNA (miRNA) Open Array and small RNA sequencing, and retinal single cell sequencing were performed, with datasets integrated and analysed computationally. Results demonstrated that exogenous transfer of neuronal miRNA to glial cells was mediated by EV and occurred as a targeted response during degeneration to modulate gliotic inflammation. Taken together, our results support a model of neuronal-to-glial communication via EV, which could be harnessed for therapeutic targeting to slow the progression of retinal-, and neuro-degenerations of the CNS.
Publisher
Wiley
Keywords
Mice; Animals; Multiomics; *Extracellular Vesicles; Neurons/metabolism; *MicroRNAs/genetics/metabolism; Inflammation/metabolism; central nervous system; extracellular vesicles; glia; neurodegeneration; retina; tissue-cross talk
Department(s)
Laboratory Research
Open Access at Publisher's Site
https://doi.org/10.1002/jev2.12393
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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