title: Next-generation sequencing-based small RNA profiling of cerebrospinal fluid exosomes.
abstract: MicroRNAs (miRNAs), particularly those found in human body fluids, have been suggested as potential biomarkers. Among various body fluids, the cerebrospinal fluid (CSF) shows promise as a profiling target for diagnosis and monitoring of neurological diseases. However, relevant genome-scale studies are limited and no studies have profiled exosomal miRNAs in CSF. Therefore, we conducted a next-generation sequencing-based genome-wide survey of small RNAs in the exosomal and non-exosomal (supernatant) fractions of healthy human CSF as well as serum in each donor. We observed miRNA enrichment in the exosomal fractions relative to the supernatant fractions of both CSF and serum. We also observed substantial differences in exosomal miRNA profiles between CSF and serum. Half of the reported brain miRNAs were found in CSF exosomal fractions. In particular, miR-1911-5p, specifically expressed in brain tissue, was detected in CSF but not in serum, as confirmed by digital PCR in three additional donors. Our data suggest that the brain is a major source of CSF exosomal miRNAs. Here we provide the important evidence that exosomal miRNAs in CSF may reflect brain pathophysiology.
authors: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan; Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors: Yohsuke
authors: Y
authors: Yagi
authors: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan; Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors: Takuya
authors: T
authors: Ohkubo
authors: RIKEN Preventive Medicine and Diagnosis Innovation Program, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; RIKEN Advanced Center for Computing and Communication, Preventive medicine and applied genomics unit, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; RIKEN Omics Science Center, Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Hideya
authors: H
authors: Kawaji
authors: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan; Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors: Akira
authors: A
authors: Machida
authors: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan; Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors: Haruka
authors: H
authors: Miyata
authors: RIKEN Omics Science Center, Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Saori
authors: S
authors: Goda
authors: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; RIKEN Omics Science Center, Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Sugata
authors: S
authors: Roy
authors: RIKEN Preventive Medicine and Diagnosis Innovation Program, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; RIKEN Omics Science Center, Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Yoshihide
authors: Y
authors: Hayashizaki
authors: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; RIKEN Omics Science Center, Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Harukazu
authors: H
authors: Suzuki
authors: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan; Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan. Electronic address: tak-yokota.nuro@tmd.ac.jp.
authors: Takanori
authors: T
authors: Yokota
mesh_terms: D001921:Brain / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000134:cerebrospinal fluid*; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs
keywords: Cerebrospinal fluid; Digital PCR; Exosome; Next-generation sequencing; Small RNA; microRNA