{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337485/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337485"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RAI1 safeguards fidelity and tempo of human neurodevelopmental gene expression","description":"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.","dates":{"publication":"2026/07/08"},"accession":"GSE337485","cross_references":{"GSM":["GSM9856239","GSM9856238","GSM9856259","GSM9856237","GSM9856258","GSM9856236","GSM9856235","GSM9856257","GSM9856278","GSM9856256","GSM9856234","GSM9856255","GSM9856233","GSM9856277","GSM9856232","GSM9856276","GSM9856254","GSM9856275","GSM9856253","GSM9856231","GSM9856252","GSM9856274","GSM9856273","GSM9856251","GSM9856272","GSM9856250","GSM9856271","GSM9856270","GSM9856249","GSM9856248","GSM9856269","GSM9856247","GSM9856246","GSM9856268","GSM9856267","GSM9856245","GSM9856266","GSM9856244","GSM9856265","GSM9856243","GSM9856264","GSM9856242","GSM9856241","GSM9856263","GSM9856262","GSM9856240","GSM9856261","GSM9856260"],"GPL":["24676"],"GSE":["337485"],"taxon":["Homo sapiens"]}}