{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336167/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"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=GSE336167"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RAI1 safeguards fidelity and tempo of human neurodevelopmental gene expression [RNA-seq]","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":"GSE336167","cross_references":{"GSM":["GSM9829359","GSM9829371","GSM9829350","GSM9829372","GSM9829370","GSM9829357","GSM9829358","GSM9829355","GSM9829356","GSM9829353","GSM9829375","GSM9829376","GSM9829354","GSM9829373","GSM9829351","GSM9829374","GSM9829352","GSM9829348","GSM9829349","GSM9829360","GSM9829361","GSM9829368","GSM9829346","GSM9829369","GSM9829347","GSM9829366","GSM9829344","GSM9829345","GSM9829367","GSM9829342","GSM9829364","GSM9829365","GSM9829343","GSM9829362","GSM9829341","GSM9829363"],"GPL":["34284"],"GSE":["336167"],"taxon":["Homo sapiens"]}}