Exosomes regulate neurogenesis and circuit assembly

Exosomes are thought to be released by all cells in the body and to be involved in intercellular communication. We tested whether neural exosomes can regulate the development of neural circuits. We show that exosome treatment increases proliferation in developing neural cultures and in vivo in denta...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2019-08, Vol.116 (32), p.16086-16094
Main Authors: Sharma, Pranav, Mesci, Pinar, Carromeu, Cassiano, McClatchy, Daniel R., Schiapparelli, Lucio, Yates, John R., Muotri, Alysson R., Cline, Hollis T.
Format: Article
Language:English
Subjects:
Action Potentials
Animals
Biological activity
Biological Sciences
Brain
Cell Count
Cell Differentiation
Cell interactions
Cell Proliferation
Cell signaling
Cells, Cultured
Circuits
Dentate gyrus
Dentate Gyrus - cytology
Exosomes
Exosomes - metabolism
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
MeCP2 protein
Methyl-CpG binding protein
Methyl-CpG-Binding Protein 2 - deficiency
Methyl-CpG-Binding Protein 2 - metabolism
Mice
Nerve Net - metabolism
Neural networks
Neurodevelopmental disorders
Neurogenesis
Neurons - cytology
Neurons - metabolism
PNAS Plus
Rett syndrome
Signal Transduction
Signaling
Spheroids, Cellular - cytology
Synapses - metabolism
Synaptogenesis
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Summary:Exosomes are thought to be released by all cells in the body and to be involved in intercellular communication. We tested whether neural exosomes can regulate the development of neural circuits. We show that exosome treatment increases proliferation in developing neural cultures and in vivo in dentate gyrus of P4 mouse brain. We compared the protein cargo and signaling bioactivity of exosomes released by hiPSC-derived neural cultures lacking MECP2, a model of the neurodevelopmental disorder Rett syndrome, with exosomes released by isogenic rescue control neural cultures. Quantitative proteomic analysis indicates that control exosomes contain multiple functional signaling networks known to be important for neuronal circuit development. Treating MECP2-knockdown human primary neural cultures with control exosomes rescues deficits in neuronal proliferation, differentiation, synaptogenesis, and synchronized firing, whereas exosomes from MECP2-deficient hiPSC neural cultures lack this capability. These data indicate that exosomes carry signaling information required to regulate neural circuit development.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1902513116