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Functional maturation of human iPSC-derived pyramidal neurons in vivo is dependent on proximity with the host tissue

Human induced pluripotent stem cells (hiPSCs) have been used extensively to model early events in neurodevelopment. Because of a number of shortcomings, previous work has established a potential to use these cells after transplantation into the mouse brain. Here, we describe a systematic approach fo...

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Bibliographic Details
Published in:Frontiers in cellular neuroscience 2023-11, Vol.17 (17), p.1259712-1259712
Main Authors: Raïs, Célia, Gaspar Santos, Daniela, Sansone, Giulia, Blanchard, Stéphane, Bourgeois, Jean-Pierre, Jagla, Bernd, Saudemont, Baptiste, Schlick, Laurène, Pons, Stéphanie, Maskos, Uwe
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Language:English
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Summary:Human induced pluripotent stem cells (hiPSCs) have been used extensively to model early events in neurodevelopment. Because of a number of shortcomings, previous work has established a potential to use these cells after transplantation into the mouse brain. Here, we describe a systematic approach for the analysis of transplanted hiPSC-derived neurons and glial cells over time in the mouse brain. Using functional two-photon imaging of GCaMP6f- expressing human neural cells, we define and quantify the embryonic-like features of their spontaneous activity. This is substantiated by detailed electron microscopy (EM) of the graft. We relate this to the synaptic development the neurons undergo up to 7 months This system can now be used further for the genetic or experimental manipulation of developing hiPSC-derived cells addressing neurodevelopmental diseases like schizophrenia or Autism Spectrum Disorder.
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2023.1259712