title: Convective exosome-tracing microfluidics for analysis of cell-non-autonomous neurogenesis.
abstract: The effective role of exosome delivering neurogenic microRNA (miRNA) enables to induce efficient differentiation process during neurogenesis. The microfludic system capable of visualizing the exosomal behavior such as secretion, migration, and uptake of individual exosomes can be used as a robust technique to understand the exosome-mediated change of cellular behavior. Here, we developed the exosome-tracing microfluidic system to visualize exosomal transport carrying the neurogenic miRNA from leading to neighboring cells, and found a new mode of exosome-mediated cell-non-autonomous neurogenesis. The miR-193a facilitated neurogenesis in F11 cells by blocking proliferation-related target genes. In addition to time-lapse live-cell imaging using microfluidics visualized the convective transport of exosomes from differentiated to undifferentiated cells. Individual exosomes containing miR-193a from differentiated donor cells were taken up by undifferentiated cells to lead them to neurogenesis. Induction of anti-miR-193a was sufficient to block neurogenesis in F11 cells. Inhibition of the exosomal production by manumycin-A and treatment of anti-miR-193a in the differentiated donor cells failed to induce neurogenesis in undifferentiated recipient cells. These findings indicate that exosomes of neural progenitors and neurogenic miRNA within these exosomes propagate cell-non-autonomous differentiation to neighboring progenitors, to delineate the roles of exosome mediating neurogenesis of population of homologous neural progenitor cells.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea; School of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Oh
authors.affiliation: School of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Yoojin
authors.initials: Y
authors.lastname: Shin
authors.affiliation: School of Mechanical Engineering, Korea University, Seoul, Republic of Korea. Electronic address: sidchung@gmail.com.
authors.forename: Seok
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea. Electronic address: hdw6592@hanmail.net.
authors.forename: Do Won
authors.initials: DW
authors.lastname: Hwang
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea. Electronic address: dsl@plaza.snu.ac.kr.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D002469:Cell Separation / Q000295:instrumentation; D002478:Cells, Cultured; D004867:Equipment Design; D005089:Exocytosis / Q000502:physiology*; D055354:Exosomes / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D056656:Lab-On-A-Chip Devices; D035683:MicroRNAs / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats
chemical_list: D035683:MicroRNAs
keywords: Cell-non-autonomous; Exosome imaging; MiR-193a; Microfluidic platform; Neurogenesis