Abstract
The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Extracellular vesicles (EVs) are cell-derived nano-sized vesicles, carrying nucleic acids, proteins, lipids, and other bioactive substances. As reported, serum neural cell adhesion molecule L1 (L1CAM)-captured EVs (LCEVs) can provide reliable biomarkers for neurological diseases; however, little is known about the LCEVs in children with ASD. The study enrolled 100 children with ASD (2.5–6 years of age; 90 males) and 60 age-matched TD children (54 males) as control. The serum sample was collected and pooled into five ASD subgroups and three TD subgroups (n = 20). LCEVs were isolated and characterized meticulously. Whole-transcriptome of LCEVs was analyzed by lncRNA microarray and RNA-sequencing. All raw data was submitted on GEO Profiles, and GEO accession numbers is GSE186493. RNAs expressed differently in LCEVs from ASD sera vs. TD sera were screened, analyzed, and further validated. A total of 1418 mRNAs, 1745 lncRNAs, and 11 miRNAs were differentially expressed, and most of them were downregulated in ASD. Most RNAs were involved in neuron- and glycan-related networks implicated in ASD. The levels of EDNRA, SLC17A6, HTR3A, OSTC, TMEM165, PC-5p-139289_26, and hsa-miR-193a-5p were validated in at least 15 ASD and 15 TD individual serum samples, which were consistent with the results of transcriptome analysis. In conclusion, whole-transcriptome analysis of serum LCEVs reveals neural and glycosylation changes in ASD, which may help detect predictive biomarkers and molecular mechanisms of ASD, and provide reference for diagnoses and therapeutic management of the disease.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ASD:
-
Autism spectrum disorder
- EVs:
-
Extracellular vesicles
- L1CAM:
-
Neural cell adhesion molecule L1
- LCEVs:
-
L1CAM-captured extracellular vesicles
- TD:
-
Typically developed
- DSM:
-
Diagnostic and Statistical Manual of Mental Disorders
- APOD:
-
Apolipoprotein D
- DBS − 2:
-
Dulbecco’s balanced salt solution
- SDS:
-
Sodium dodecyl sulfonate
- qRT-PCR:
-
Quantitative real-time PCR
- HCA:
-
Hierarchical clustering analysis
- PCA:
-
Principal component analysis
- DEmRs:
-
Differentially expressed mRNAs
- DElnRs:
-
Differentially expressed lncRNAs
- DEmiRs:
-
Differentially expressed miRNAs
- HTR3A:
-
5-Hydroxytryptamine receptor 3A
- SERT:
-
Serotonin transporter
- SLC17A6:
-
Vesicular glutamate transporter 2
- Glu:
-
Glutamate
- ECM:
-
Extracellular matrix
- CDGs:
-
Congenital glycosylation disorders
- OST:
-
Oligosaccharyl transferase
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Acknowledgements
The authors sincerely thank all the participants.
Funding
This work was supported by the National Natural Science Foundation of China(No. 81401137 and No. 81972603), and the Natural Science Foundation of Shaanxi Province (No.2017JM8112).
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Y.Q. carried out analysis of data from lncRNA microarray and RNA sequencing, generated the graphs, and wrote the manuscript; L.C. took charge of preparation of serum samples, isolation and characterization of serum LCEVs, and qRT-PCR; J.Z. took on the data analysis, graphing, and manuscript revision; H.Z. collected samples from patients and summarize the clinical information of patients; S.C. and L.Z. participated in data analysis; B.G. performed extraction of LCEVs; F.W., W.L., and X.W. participated in bioinformatics analysis; L.N. and L.L. modified the draft of this paper; Y.C. performed ASD diagnosis and sample collection; and C.H. participated in the design of the project, coordination of the staff, and revision of the manuscript. All authors read and approved the final manuscript.
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Qin, Y., Cao, L., Zhang, J. et al. Whole-Transcriptome Analysis of Serum L1CAM-Captured Extracellular Vesicles Reveals Neural and Glycosylation Changes in Autism Spectrum Disorder. J Mol Neurosci 72, 1274–1292 (2022). https://doi.org/10.1007/s12031-022-01994-z
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DOI: https://doi.org/10.1007/s12031-022-01994-z