{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303838/"]},"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=GSE303838"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MECP2 Mutations Rewire Human ESC Fate and Bias Cortical Lineage Commitment [RNA-Seq]","description":"Rett syndrome arises from loss-of-function mutations in the X-linked chromatin regulator MECP2, yet the earliest molecular derailments in human development remain poorly defined. Using isogenic hESC models carrying three patient-derived MECP2 mutations, we followed the transcriptome from pluripotency through neuro-ectoderm, neural stem, and neural progenitor stages and into four-month cerebral organoids. Stage dominated transcriptional variance, but mutants shared a secondary program enriched for synaptic-membrane and extracellular-matrix genes. Single-cell profiling revealed a naïve-like, hyper-proliferative state marked by up-regulation of ZFP42 at ESC stage. Strikingly, EMX1, a cortical radial-glia determinant, was consistently suppressed from the earliest stage onward, and cerebral organoids subsequently generated fewer excitatory neurons in favour of inhibitory and glial lineages. These data chart a continuous developmental trajectory for MECP2-mutant human cells and nominate ZFP42 and EMX1 dysregulation as tractable entry points for dissecting Rett pathogenesis.","dates":{"publication":"2026/04/23"},"accession":"GSE303838","cross_references":{"GSM":["GSM9136780","GSM9136782","GSM9136760","GSM9136781","GSM9136762","GSM9136784","GSM9136783","GSM9136761","GSM9136786","GSM9136764","GSM9136785","GSM9136763","GSM9136788","GSM9136766","GSM9136765","GSM9136787","GSM9136768","GSM9136801","GSM9136800","GSM9136789","GSM9136767","GSM9136803","GSM9136802","GSM9136769","GSM9136791","GSM9136790","GSM9136771","GSM9136793","GSM9136792","GSM9136770","GSM9136795","GSM9136773","GSM9136794","GSM9136772","GSM9136797","GSM9136775","GSM9136774","GSM9136796","GSM9136799","GSM9136777","GSM9136798","GSM9136776","GSM9136779","GSM9136778","GSM9136759","GSM9136805","GSM9136804","GSM9136806"],"GPL":["34281"],"GSE":["303838"],"taxon":["Homo sapiens"]}}