Frontiers in Cellular Neuroscience (Nov 2023)

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

  • Célia Raïs,
  • Célia Raïs,
  • Daniela Gaspar Santos,
  • Daniela Gaspar Santos,
  • Giulia Sansone,
  • Stéphane Blanchard,
  • Jean-Pierre Bourgeois,
  • Bernd Jagla,
  • Baptiste Saudemont,
  • Laurène Schlick,
  • Stéphanie Pons,
  • Uwe Maskos

DOI
https://doi.org/10.3389/fncel.2023.1259712
Journal volume & issue
Vol. 17

Abstract

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Human induced pluripotent stem cells (hiPSCs) have been used extensively in vitro to model early events in neurodevelopment. Because of a number of shortcomings, previous work has established a potential to use these cells in vivo 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 in vivo. 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.

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