Radiofrequency regulates the BET-mediated pathways in radial glia differentiation in human cortical development

The human brain represents one of the most complex organs in our body, with development regulated by an intricate genetic program. Recently, non-genetic factors, such as prenatal stress, infection, and diet, have been shown to influence brain development. Radiofrequency radiation (RF; 800-2,400 MHz), emitted by natural and artificial sources such as microwaves and cell phones, represents a non-invasive environmental factor. Using human cortical organoids (hCOs) derived from human embryonic stem cells (hESCs), we investigate RF's effects on corticogenesis. We find that RF exposure regulates the differentiation of human and non-human primate radial glia progenitors, maintaining stem cell identity and delaying differentiation. Neurons differentiated under RF treatment show induction of expression of human endogenous retroviruses. Importantly, inhibitors for the BET (bromodomain and extraterminal) protein rescue RF-induced developmental defects in hCOs. Our findings reveal a mechanism by which RF modulates early brain development, offering a non-biological approach to regulate neural stem cell self-renewal.