Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets.
Greta PintacudaJacqueline M MartínKevin C EgganPublished in: Molecular autism (2021)
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by impaired social interactions as well as the presentation of restrictive and repetitive behaviors. ASD is highly heritable but genetically heterogenous with both common and rare genetic variants collaborating to predispose individuals to the disorder. In this review, we synthesize recent efforts to develop human induced pluripotent stem cell (iPSC)-derived models of ASD-related phenotypes. We firstly address concerns regarding the relevance and validity of available neuronal iPSC-derived models. We then critically evaluate the robustness of various differentiation and cell culture protocols used for producing cell types of relevance to ASD. By exploring iPSC models of ASD reported thus far, we examine to what extent cellular and neuronal phenotypes with potential relevance to ASD can be linked to genetic variants found to underlie it. Lastly, we outline promising strategies by which iPSC technology can both enhance the power of genetic studies to identify ASD risk factors and nominate pathways that are disrupted across groups of ASD patients that might serve as common points for therapeutic intervention.
Keyphrases
- autism spectrum disorder
- attention deficit hyperactivity disorder
- intellectual disability
- stem cells
- induced pluripotent stem cells
- risk factors
- randomized controlled trial
- end stage renal disease
- cell therapy
- ejection fraction
- healthcare
- endothelial cells
- gene expression
- mental health
- prognostic factors
- peritoneal dialysis
- copy number
- high glucose
- high frequency
- working memory
- human health
- climate change
- risk assessment
- dna methylation
- mesenchymal stem cells
- case report
- resting state