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

Célia Raïs (1, 2) , Daniela Gaspar Santos (1, 2) , Giulia Sansone (1) , Stéphane Blanchard (1) , Jean-Pierre Bourgeois (3, 4) , Bernd Jagla (4) , Baptiste Saudemont (4) , Laurène Schlick (1) , Stéphanie Pons (1) , Uwe Maskos (1)

1 NISC - Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems
2 Collège Doctoral
3 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
4 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB

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.

Domaines: Neurosciences

Célia Raïs, Daniela Gaspar Santos, Giulia Sansone, Stéphane Blanchard, Jean-Pierre Bourgeois, et al.. Functional maturation of human iPSC-derived pyramidal neurons in vivo is dependent on proximity with the host tissue. Frontiers in Cellular Neuroscience, 2023, 23 (17), pp.1259712. ⟨10.3389/fncel.2023.1259712⟩. ⟨pasteur-04511558⟩