GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336167/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336167GEOGSEfalseRAI1 safeguards fidelity and tempo of human neurodevelopmental gene expression [RNA-seq]Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.2026/07/08GSE336167GSM9829359GSM9829371GSM9829350GSM9829372GSM9829370GSM9829357GSM9829358GSM9829355GSM9829356GSM9829353GSM9829375GSM9829376GSM9829354GSM9829373GSM9829351GSM9829374GSM9829352GSM9829348GSM9829349GSM9829360GSM9829361GSM9829368GSM9829346GSM9829369GSM9829347GSM9829366GSM9829344GSM9829345GSM9829367GSM9829342GSM9829364GSM9829365GSM9829343GSM9829362GSM9829341GSM982936334284336167Homo sapiens