Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction

Author:

Cheffer Arquimedes,Flitsch Lea JessicaORCID,Krutenko Tamara,Röderer Pascal,Sokhranyaeva Liubov,Iefremova Vira,Hajo Mohamad,Peitz MichaelORCID,Schwarz Martin Karl,Brüstle OliverORCID

Abstract

AbstractThe controlled differentiation of pluripotent stem cells (PSCs) into neurons and glia offers a unique opportunity to study early stages of human central nervous system development under controlled conditions in vitro. With the advent of cell reprogramming and the possibility to generate induced pluripotent stem cells (iPSCs) from any individual in a scalable manner, these studies can be extended to a disease- and patient-specific level. Autism spectrum disorder (ASD) is considered a neurodevelopmental disorder, with substantial evidence pointing to early alterations in neurogenesis and network formation as key pathogenic drivers. For that reason, ASD represents an ideal candidate for stem cell-based disease modeling. Here, we provide a concise review on recent advances in the field of human iPSC-based modeling of syndromic and non-syndromic forms of ASD, with a particular focus on studies addressing neuronal dysfunction and altered connectivity. We further discuss recent efforts to translate stem cell-based disease modeling to 3D via brain organoid and cell transplantation approaches, which enable the investigation of disease mechanisms in a tissue-like context. Finally, we describe advanced tools facilitating the assessment of altered neuronal function, comment on the relevance of iPSC-based models for the assessment of pharmaceutical therapies and outline potential future routes in stem cell-based ASD research.

Funder

Horizon 2020

ERA-Net Neuron program

The European Regional Development Fund

The Federal Institute for Drugs and Medical Devices

Projekt DEAL

Publisher

Springer Science and Business Media LLC

Subject

Psychiatry and Mental health,Developmental Biology,Developmental Neuroscience,Molecular Biology

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