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

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

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1259712

DOI=10.3389/fncel.2023.1259712

ISSN=1662-5102

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