REST deficiency and neurogenic-to-gliogenic shift in Down syndrome human cerebral organoids

This study identifies REST protein dysfunction at a specific developmental window (DIV-90) as a key driver of impaired neurogenesis and excess gliogenesis in Down syndrome using multi-omics and machine learning analysis of human cerebral organoids. The findings reveal REST-regulated hub genes and signaling pathways (NFIA/STAT3) that control neural cell fate, suggesting potential targets for early developmental intervention in Down syndrome.