Modeling Pediatric Epilepsy Through iPSC-Based Technologies

Abstract

In the current review, we discuss the process of modeling pediatric epileptic encephalopathies with a focus on in vitro iPSC-based technologies. We highlight the potential benefits as well as the challenges of these approaches and propose appropriate standards for the field.

FIGURE 1.

Number of mutations identified in epilepsy genes by gene function. One hundred twenty-one epilepsy-associated genes were compiled from the EGI epilepsy gene list (https://www.cureepilepsy.org/egi/genes.asp, see [5, 15, 50]). Genes were categorized using GO slim biological function terms and the number of mutations identified in a gene was compiled from querying HGMD professional database.

FIGURE 2.

Schematic of iPSC in vitro modeling assays. Isogenic controls are generated using CRISPR/Cas9 gene editing. iPSCs can be differentiated into distinct cellular subtypes such as excitatory neurons, inhibitory neurons, astrocytes, as well as multicellular, 3-dimensional organoids.