16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis

Tomasello DL, Kim JL, Khodour Y, McCammon JM, Mitalipova M, Jaenisch R, Futerman AH, and Sive H.

iScience, 2021.


Scientists using human cells and zebrafish models provide new insights into the role the FAM57B gene plays in 16p11.2 Deletion Syndrome (16pdel)

The genetic condition 16p11.2 Deletion Syndrome (16pdel), which is estimated to affect about one in 2,500 globally, is associated with developmental delay, intellectual disability, autism spectrum disorder, attention deficit-hyperactivity disorder, epilepsy, and other concerns. In this study, scientists used neurons from 16pdel carrier induced-pluripotent stem cells (iPSC) and zebrafish models to demonstrate augmented local field potential activity and explore the potential role of FAM57B in lipid metabolism and neural development. Previous evidence suggests the FAM57B gene plays a role in 16pdel symptomatology, but this relationship has not been well understood.

To examine network activity in the iPSC-derived neurons, the researchers used Axion’s Maestro multielectrode array (MEA) platform and found that the 16pdel neurons displayed increased spontaneous and evoked activity. Sex differences were also observed, with results showing heightened electrical activity in female 16pdel neuron cultures compared to males. In additional MEA testing to examine brain development over time, zebrafish larvae with the variant demonstrated severely diminished spontaneous brain activity, which the authors linked to other findings suggesting a role for FAM57B in the regulation of brain function by modulating ceramide synthase. Taken together, these findings show that the deletion of FAM57B may contribute to altered neuronal activity and function in 16pdel Syndrome via the gene’s critical role in lipid metabolism.