Tissue- and cell-type-specific molecular and functional signatures of 16p11.2 reciprocal genomic disorder across mouse brain and human neuronal models

Tai D, Razaz P, Erdin S, Gao D, Wang J, Nuttle X, de Esch CE, Collins RL, Currall BB, O’Keefe K, Burt ND, Yadav R, Wang L, Mohajeri K, Aneichyk T, Ragavendran A, Stortchevoi A, Morini E, Ma W, Lucente D, Hastie A, Kelleher RJ, Perlis RH, Talkowski ME, Gusella JF

Cell, 2022


Scientists use Axion’s MEA platform to examine electrical activity in CRISPR-generated hiPSC-derived neurons in vitro

The 16p11.2 reciprocal genomic disorder involving the deletion or duplication of a contiguous set of genes is associated with neurodevelopmental and neuropsychiatric conditions including developmental delay, intellectual disability, autism spectrum disorder, attention deficit-hyperactivity disorder, epilepsy, and schizophrenia. In this study, scientists use mouse models and CRISPR-generated human induced pluripotent stem cell (hiPSC)-derived neurons and organoids to explore the impact of the disorder on genome-wide gene expression and cellular function. Using Axion’s noninvasive, label-free Maestro multielectrode array (MEA) platform, along with other testing methods, the researchers demonstrated that 16p11.2 mutations disrupt gene expression and alter excitatory/inhibitory balance, both of which may contribute to disease phenotypes.