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Table 3 Phenotypic analyses of ASD iPSC-derived neurons : Rett, Phelan-Mcdermid, Timothy, Fragile-X, and Angelman Syndromes

From: Understanding the molecular basis of autism in a dish using hiPSCs-derived neurons from ASD patients

Diseases Related genes Neural differentiation methods Identity of neurons Electrophysiological proterties Neurodevelopmental phenotypes References
Rett syndrome Methyl CpG binding protein 2 (MECP2) Embryoid body formation Gluramatergic & gabaergic neurons Reduced sEPSC and sIPSC Fewer synaptic conracts; reduced cell soma size and dendritic branching and spine density Marchetto et al. 2010 [104]; Cheung et al. 2011 [105]; Kim et al. 2011 [106]
Phelan-McDermid Syndrome (PMDS) (22q13 deletion syndrome) Shank3 Dual smad inhibition Forebrain neurons Reduced excitatory synaptic transmission Reduced glutamatergic receptors; decreased number of synapses Shcheglovitov et al. 2013 [117]
Timothy syndrome (A member of the long QT syndromes) CACNA1 (alpha-1 subunit of the L-type calcium channel CaV1.2) Embryoid body formation Cortical-enriched neuronal populations Increase in the sustained intracellular calcium rise following membrane depolarization; wider action potentials Decreased expression of lower corticallayers-related genes; increases in TH (tyrosine hydroxylase)-, norepinephrine- and dopamine-positice cells; activity-dependent dendrite retraction Pasca et al. 2011 [107]; Krey et al. 2013 [108]
Fragile X syndrome Fragile X mental retardation 1 (FMR1) Embryoid body formation Tuj1-, MAP2- or GFAP-positive cells Poor spontaneous synaptic activity and no glutamate reactivity Reduced neurite numbers and neurite lengths; reduced PSD95 protein expression and reduced synaptic punctadensity; poor neuronal maturation and high gliogenic development Sheridan et al. 2011 [109]; Telias et al. 2013 [110]
Angelman syndrome Ubiquitin protein ligase E3A (UBE3A) Embryoid body formation Tuj1-positive cells Normal electrophysiological properties Intact imprinting of UBE3A Chamberlain et al. 2010 [111]