{"database":"GEO","file_versions":[],"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=GSE303977"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MECP2 Mutations Rewire Human ESC Fate and Bias Cortical Lineage Commitment II","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":"GSE303977","cross_references":{"GSM":["GSM9140078","GSM9140079","GSM9140077","GSM9140081","GSM9140082","GSM9140083","GSM9140084","GSM9140080"],"GPL":["34281"],"GSE":["303977"],"taxon":["Homo sapiens"]}}