Transcriptomic Signatures of Neuronally-Derived Extracellular Vesicles Reveals Presence of Olfactory Receptors in Clinical Samples of Traumatic Brain Injury Patients
Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. Recently, the FDA has approved blood-based biomarkers, GFAP and UCH-L1, to evaluate the need for CT scans, however, clinical translation is currently limited. Exosomes are small microcellular vesicles which are released from the cell in both normal and diseased states, as part of extracellular communication. The aim of this study was to isolate neuronal exosomes derived from the serum of patients with severe TBI and characterize the messenger RNA content of the exosomes released by the injured neurons in order to identify new potential blood-based biomarkers. RNA was isolated from neuronal exosomes and total transcriptomic sequencing was performed. RNA sequencing data from neuronal exosomes isolated from serum showed mRNA transcripts of several neuronal genes. Additionally, the RNA sequencing data revealed mRNA of several olfactory receptor genes, which were present at elevated concentrations in the neuronal exosomes. Further validation in serum samples of mild TBI patients revealed a similar upregulation of olfactory receptors. The data from these experiments suggests that damage to the neurons in the olfactory neuroepithelium and in the brain, following a TBI, may cause the release of mRNA from these receptors in the exosomes. Thus, olfactory receptors can be further investigated as potential biomarkers for TBI diagnosis. Overall design: To characterize the transcriptome of neuronally derived exosomes, we first isolated neuronal exosomes from serum of patients with severe TBI RNA was exracted from the neuronal exosomes and cleaved RNA fragments were reverse-transcribed to create the final cDNA library in accordance with dUTP methods.