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Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS.
Nat Commun 2019; 10(1):4136NC

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.

Authors+Show Affiliations

Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA. Tufts University, Sackler School of Biomedical Sciences, 136 Harrison Avenue, Boston, MA, 02111, USA.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA. Dongfang Hospital of University of Chinese Medicine, No.6, District 1, Fangxingyuan, Fangzhuang, Fengtai District, 100078, Beijing, People's Republic of China.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA.Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA, 02111, USA. yongjie.yang@tufts.edu. Tufts University, Sackler School of Biomedical Sciences, 136 Harrison Avenue, Boston, MA, 02111, USA. yongjie.yang@tufts.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31515491

Citation

Men, Yuqin, et al. "Exosome Reporter Mice Reveal the Involvement of Exosomes in Mediating Neuron to Astroglia Communication in the CNS." Nature Communications, vol. 10, no. 1, 2019, p. 4136.
Men Y, Yelick J, Jin S, et al. Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS. Nat Commun. 2019;10(1):4136.
Men, Y., Yelick, J., Jin, S., Tian, Y., Chiang, M. S. R., Higashimori, H., ... Yang, Y. (2019). Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS. Nature Communications, 10(1), p. 4136. doi:10.1038/s41467-019-11534-w.
Men Y, et al. Exosome Reporter Mice Reveal the Involvement of Exosomes in Mediating Neuron to Astroglia Communication in the CNS. Nat Commun. 2019 Sep 12;10(1):4136. PubMed PMID: 31515491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS. AU - Men,Yuqin, AU - Yelick,Julia, AU - Jin,Shijie, AU - Tian,Yang, AU - Chiang,Ming Sum R, AU - Higashimori,Haruki, AU - Brown,Eoin, AU - Jarvis,Rachel, AU - Yang,Yongjie, Y1 - 2019/09/12/ PY - 2018/11/13/received PY - 2019/07/10/accepted PY - 2019/9/14/entrez PY - 2019/9/14/pubmed PY - 2019/9/14/medline SP - 4136 EP - 4136 JF - Nature communications JO - Nat Commun VL - 10 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/31515491/Exosome_reporter_mice_reveal_the_involvement_of_exosomes_in_mediating_neuron_to_astroglia_communication_in_the_CNS L2 - http://dx.doi.org/10.1038/s41467-019-11534-w DB - PRIME DP - Unbound Medicine ER -