Whole-transcriptome analysis of serum neuron-derived exosomes reveals specific signature for autism spectrum disorder in Chinese children

Abstract BackgroundAutism spectrum disorder (ASD) is a prevalent developmental disorder that appears in early childhood and manifests repetitive behavioral and social deficits. Reported biomarkers for ASD cannot directly and specifically reflect the abnormality of brain neurons which are preferentially affected and correlated with clinical severity of the disease. Neuron-derived exosomes (NDEs), which carry proteins, lipids and nucleic acids can reflect a variety of brain diseases. However, little research has been reported about NDEs in children with ASD. MethodsSerum samples were collected from 100 ASD children and 60 age-matched typically developed (TD) children, and were pooled into 5 ASD groups and 3 TD groups (n=20). NDEs from the pooled sera in each group were isolated using L1CAM antibody mediated immunosorbent assay and characterized by nanoparticle tracking analysis, transmission electron microscopy and western blot. Whole-transcriptome of NDEs was detected by lncRNA microarray and RNA-Sequencing. RNAs expressed differently in NDEs from ASD sera as versus those from TD sera were screened, analyzed, and validated. ResultsSerum NDEs were isolated successfully. A total of 1418 mRNAs, 1745 lncRNAs and 11 miRNAs were identified to be differentially expressed, and most of them were down-regulated in ASD. The differentially expressed RNAs were prone to be distributed on chromosome 17. Target gene prediction and bioinformatic analysis revealed that a large portion of RNAs were involved in neuron- and glycan-related networks implicated in ASD. qRT-PCR identified that the levels of EDNRA, SLC17A6, HTR3A, OSTC, TMEM165, PC-5p-139289_26, and hsa-miR-193a-5p changed significantly in ASD, indicating them as potential biomarkers for the disease. LimitationsThe correlation between the expression of candidate biomarkers and disease severity were not examined. Some of our participants were not medication-free. Samples were mainly from a single hospital. ConclusionsWhole-transcriptome analysis of serum NDEs reveals specific signature for ASD in Chinese children, which may help detect predictive biomarkers and molecular mechanisms of ASD, and provide reference for diagnoses and therapeutic management of the disease.