Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment

To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using CRISPR toll and then generated cortical organoids. This modification promoted several phenotypes, including slower organoid development and higher surface complexity with the archaic version of NOVA1.To investigate the molecular modifications, cells were subjected to Whole exome (WES) and transcriptome (RNA-seq) sequencing, eClip and snRNA-seq.