Neural Stem Cell-Derived Exosomes Regulate Neural Stem Cell Differentiation Through miR-9-Hes1 Axis

Ping Yuan, Lu Ding, Huili Chen, Yi Wang, Chunhong Li, Shu Zhao, Xiaoyu Yang, Yizhao Ma, Jie Zhu, Xinrui Qi, Yanyan Zhang, Xiaohuan Xia, Jialin C. Zheng

Research output: Contribution to journalArticlepeer-review

Abstract

Exosomes, a key element of the central nervous system microenvironment, mediate intercellular communication via horizontally transferring bioactive molecules. Emerging evidence has implicated exosomes in the regulation of neurogenesis. Recently, we compared the neurogenic potential of exosomes released from primary mouse embryonic neural stem cells (NSCs) and astrocyte-reprogrammed NSCs, and observed diverse neurogenic potential of those two exosome populations in vitro. However, the roles of NSC-derived exosomes on NSC differentiation and the underlying mechanisms remain largely unknown. In this study, we firstly demonstrated that NSC-derived exosomes facilitate the differentiation of NSCs and the maturation of both neuronal and glial cells in defined conditions. We then identified miR-9, a pro-neural miRNA, as the most abundantly expressed miRNA in NSC-derived exosomes. The silencing of miR-9 in exosomes abrogates the positive effects of NSC-derived exosomes on the differentiation of NSCs. We further identified Hes1 as miR-9 downstream target, as the transfection of Hes1 siRNA restored the differentiation promoting potential of NSC-derived exosomes after knocking down exosomal miR-9. Thus, our data indicate that NSC-derived exosomes facilitate the differentiation of NSCs via transferring miR-9, which sheds light on the development of cell-free therapeutic strategies for treating neurodegeneration.

Original languageEnglish (US)
Article number601600
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
StatePublished - May 13 2021

Keywords

  • Hes1
  • differentiation
  • exosome
  • maturation
  • miR-9
  • miRNA
  • neural stem cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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