In vivo modeling of human neuron dynamics and Down syndrome.
Science
; 362(6416)2018 11 16.
Article
en En
| MEDLINE
| ID: mdl-30309905
ABSTRACT
Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)-derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks. Lastly, we found increased synaptic stability and reduced oscillations in transplants from two individuals with Down syndrome, demonstrating the potential of in vivo imaging in human tissue grafts for patient-specific modeling of cortical development, physiology, and pathogenesis.
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1
Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
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Síndrome de Down
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Neurogénesis
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Modelos Biológicos
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Plasticidad Neuronal
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Neuronas
Idioma:
En
Revista:
Science
Año:
2018
Tipo del documento:
Article