Distinct repertoires of microRNAs present in mouse astrocytes compared to astrocyte-secreted exosomes.
BACKGROUND
Astrocytes are the most abundant cell type in the central nervous system (CNS) and secrete various factors that regulate neuron development, function and connectivity. microRNAs (miRNAs) are small regulatory RNAs involved in posttranslational gene regulation. Recent findings showed that miRNAs are exchanged between cells via nanovesicles called exosomes. In this study, we sought to define which miRNAs are contained within exosomes secreted by astrocytes. We also explored whether astroglial miRNA secretion via exosomes is perturbed in a mouse model of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease where astrocytes play a crucial role in driving disease progression.


RESULTS
By isolating and profiling the expression of miRNAs from primary mouse astrocytes and from the exosomes that astrocytes secrete, we compared miRNA expression in the cells and secreted vesicles. We established that miRNA expression profiles of astrocytes and their exosomes are vastly different. In addition, we determined that exosomal miRNA expression in astrocytes is not significantly perturbed in a mouse model of ALS.


CONCLUSIONS
Astrocytes secrete numerous miRNAs via exosomes and miRNA species contained in exosomes are considerably different from miRNAs detectable in astrocytes, suggesting the existence of a mechanism to select certain miRNAs for inclusion or exclusion from exosomes. The exosomal miRNA profiling dataset we have generated will provide a resource to aid in the investigation of this selection mechanism. Finally, the miRNA expression profile in astrocyte-secreted exosomes is not perturbed by expression of mutant SOD1-G93A.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, United States of America.
Ana
http://orcid.org/0000-0002-7210-1404
A
Jovičić
Department of Genetics, Stanford University School of Medicine, Stanford, CA, United States of America.
Aaron D
AD
Gitler
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D059467:Transcriptome
D035683:MicroRNAs