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

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

doi:10.3389/fncel.2023.1259712

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

Front Cell Neurosci. 2023 Nov 23:17:1259712. doi: 10.3389/fncel.2023.1259712. eCollection 2023.

Authors

Affiliations

¹ Institut Pasteur, Université de Paris Cité, Unité Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS UMR 3571 "Genes, Synapses and Cognition," Paris, France.
² Collège Doctoral, Sorbonne Université, Paris, France.
³ Institut Pasteur, Université de Paris Cité, Human Genetics and Cognitive Functions, CNRS UMR 3571 "Genes, Synapses and Cognition," Paris, France.
⁴ Institut Pasteur, Université de Paris Cité, Cytometry and Biomarkers Unit of Technology and Service, Center for Translational Science and Bioinformatics and Biostatistics Hub-C3BI, Paris, France.

Abstract

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.

Keywords: electron microscopy; grafting; human induced pluripotent stem cells; neural precursor cells; neurodevelopment.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. CR and DG were Ph.D. students at Sorbonne Université, Ecole doctorale 3C. CR was funded by the Laboratory of Excellence LABEX BIOPSY and the Fondation pour la Recherche Médicale FRM (contrat FDT201805005198). Work in the NISC laboratory was supported by PasteurInnov, FRM Equipe 2019, Laboratory of Excellence LABEX BIOPSY, Fondation Alzheimer, INCa TABAC 2022, and SPA 2020, all to UM, and by Programme Explore Institut Pasteur and CNRS.