Abnormalities in migration of neural precursor cells in familial bipolar disorder

Cellular migration is a ubiquitous feature that brings brain cells into appropriate spatial relationships over time; and it helps in the formation of a functional brain. We studied the migration patterns of induced pluripotent stem cell (IPSC)-derived neural precursor cells (NPCs) from individuals with familial bipolar disorder (BD), in comparison with healthy controls. The BD patients also had morphological brain abnormalities in magnetic resonance imaging. Time-lapse analysis of migrating cells was conducted, through which we were able to identify several parameters to be abnormal in cellular migration, including the speed and directionality of NPCs. We also performed transcriptomic analysis to probe the mechanisms behind aberrant cellular phenotype identified. Our analysis showed downregulation of a network of genes, centering on EGF/ERBB proteins. Present findings indicate that collective, systemic dysregulation may produce the aberrant cellular phenotype; which could contribute to the functional and structural changes in the brain, reported in bipolar disorder.