Radiofrequency radiation impairs the human cortical organoid development

Neurodevelopmental disorders pose a severe health burden in our society, with remarkably increasing prevalence in children. Though radiofrequency radiation (RF) exposure to the prenatal brain is one of the environmental risks strongly associated with neurobehavioral disorders, its direct impact on human brain development remains largely unknown. Here we use human brain organoids representing the cortex, namely cortical organoids (hCOs) from human embryonic stem cells (hESC), to examine the effects of RF from mobile phones on corticogenesis. We found that RF exposure to brain organoids leads to structural impairment and the defective mitotic behaviors of radial glia progenitors, which carry out critical roles in neocortical expansion. We further uncovered that RF-treated organoids acquire the dysregulation in the transcriptional program, including the aberrant expression of autism risk genes and the morphologically and functionally abnormal neurons. Moreover, the RF shield made complete protection of the detrimental impact of RF on corticogenesis. Finally, we identified small molecule inhibitors for BET proteins that ameliorated RF-induced damages in cortical organoids. Our findings demonstrate how RF exposure impairs brain development and suggest new strategies to prevent RF-mediated brain damage. Overall design: Human cortical organoids were treated by mobile phone-emitted radiation and analyzed by scRNA-seq