GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303838/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303838GEOGSEfalseMECP2 Mutations Rewire Human ESC Fate and Bias Cortical Lineage Commitment [RNA-Seq]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.2026/04/23GSE303838GSM9136780GSM9136760GSM9136782GSM9136781GSM9136762GSM9136784GSM9136783GSM9136761GSM9136786GSM9136764GSM9136785GSM9136763GSM9136788GSM9136766GSM9136765GSM9136787GSM9136768GSM9136801GSM9136800GSM9136789GSM9136767GSM9136803GSM9136802GSM9136769GSM9136791GSM9136790GSM9136771GSM9136793GSM9136792GSM9136770GSM9136795GSM9136773GSM9136794GSM9136772GSM9136797GSM9136775GSM9136774GSM9136796GSM9136799GSM9136777GSM9136798GSM9136776GSM9136779GSM9136778GSM9136759GSM9136805GSM9136804GSM913680634281303838Homo sapiens