Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome

Chapman G, Alsaqati M, Lunn S, Singh T, Linden SF, Linden DEJ, van den Bree MBM, Ziller M, Owen MJ, Hall J, Harwood AJ and Syed YA.

Molecular Psychiatry, 2021



Copy Number Variation at 1q21.1 is associated with a range of neurodevelopmental and psychiatric disorders. However, the functional consequences on neuronal development of the deletions and duplications is unknown.  To investigate, the authors developed iPSC-derived functional cortical neurons from individuals with 1q21.1 deletions or duplications.  The derived cells were evaluated for proliferation, differentiation potential, neuronal maturation, synaptic density and functional activity.  The Maestro Pro MEA platform was used to evaluate neuronal network activity.  Neurons with deletions exhibited higher spike rates, frequency of bursting and earlier onset of synchrony than control neurons, while neurons with duplications did not show a significant difference from the control neurons.  Overall this study identified that 1q21.1 locus deletions increased neuronal activity and deficits in neuronal network functionality.