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Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS

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  • Yuqin Men

    (Tufts University School of Medicine, Department of Neuroscience
    Tufts University, Sackler School of Biomedical Sciences)

  • Julia Yelick

    (Tufts University School of Medicine, Department of Neuroscience)

  • Shijie Jin

    (Tufts University School of Medicine, Department of Neuroscience)

  • Yang Tian

    (Tufts University School of Medicine, Department of Neuroscience
    Dongfang Hospital of University of Chinese Medicine)

  • Ming Sum R. Chiang

    (Tufts University School of Medicine, Department of Neuroscience)

  • Haruki Higashimori

    (Tufts University School of Medicine, Department of Neuroscience)

  • Eoin Brown

    (Tufts University School of Medicine, Department of Neuroscience)

  • Rachel Jarvis

    (Tufts University School of Medicine, Department of Neuroscience)

  • Yongjie Yang

    (Tufts University School of Medicine, Department of Neuroscience
    Tufts University, Sackler School of Biomedical Sciences)

Abstract

Astroglia play active and diverse roles in modulating neuronal/synaptic functions in the CNS. How these astroglial functions are regulated, especially by neuronal signals, remains largely unknown. Exosomes, a major type of extracellular vesicles (EVs) that originate from endosomal intraluminal vesicles (ILVs), have emerged as a new intercellular communication process. By generating cell-type-specific ILVs/exosome reporter (CD63-GFPf/f) mice and immuno-EM/confocal image analysis, we found that neuronal CD63-GFP+ ILVs are primarily localized in soma and dendrites, but not in axonal terminals in vitro and in vivo. Secreted neuronal exosomes contain a subset of microRNAs (miRs) that is distinct from the miR profile of neurons. These miRs, especially the neuron-specific miR-124-3p, are potentially internalized into astrocytes. MiR-124-3p further up-regulates the predominant glutamate transporter GLT1 by suppressing GLT1-inhibiting miRs. Our findings suggest a previously undescribed neuronal exosomal miR-mediated genetic regulation of astrocyte functions, potentially opening a new frontier in understanding CNS intercellular communication.

Suggested Citation

  • Yuqin Men & Julia Yelick & Shijie Jin & Yang Tian & Ming Sum R. Chiang & Haruki Higashimori & Eoin Brown & Rachel Jarvis & Yongjie Yang, 2019. "Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11534-w
    DOI: 10.1038/s41467-019-11534-w
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    Cited by:

    1. Shijie Jin & Xuan Chen & Yang Tian & Rachel Jarvis & Vanessa Promes & Yongjie Yang, 2023. "Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Zhen-Xing Wang & Zhong-Wei Luo & Fu-Xing-Zi Li & Jia Cao & Shan-Shan Rao & Yi-Wei Liu & Yi-Yi Wang & Guo-Qiang Zhu & Jiang-Shan Gong & Jing-Tao Zou & Qiang Wang & Yi-Juan Tan & Yan Zhang & Yin Hu & Yo, 2022. "Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Bárbara Adem & Nuno Bastos & Carolina F. Ruivo & Sara Sousa-Alves & Carolina Dias & Patrícia F. Vieira & Inês A. Batista & Bruno Cavadas & Dieter Saur & José C. Machado & Dawen Cai & Sonia A. Melo, 2024. "Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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