{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302414/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302414"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RNF2 Missense Variants Disrupt Polycomb Repression and Enable Ectopic Mesenchymal Lineage Conversion During Human Neural Differentiation [CUT&RUN]","description":"Polycomb Repressive Complex 1 (PRC1) catalyzes H2AK119ub1 to facilitate transcriptional repression during development. De novo dominant missense variants in RNF2, the principal E3 ligase of PRC1, are the genetic basis of Luo-Schoch-Yamamoto syndrome. To investigate the developmental impact of catalytically impaired RNF2 alleles, we engineered hESC lines harboring homozygous hypomorphic RNF2 missense alleles (RNF2MS/MS) that stably expresses RNF2 with reduced H2AK119ub1. Upon directed neural differentiation, RNF2MS/MS cells exhibited asynchronous neural differentiation and ectopic emergence of mesenchymal fated lineages. Single-cell transcriptomic analyses revealed a fate bifurcation characterized by derepression of TWIST1 and other epithelial-to-mesenchymal transition (EMT) gene-network components, coinciding with focal loss of H2AK119ub1 and H3K27me3. These findings demonstrate that RNF2-mediated H2AK119ub1 is required to constrain lineage fidelity by repressing context-inappropriate developmental programs during early human neural differentiation, and reveal a shared chromatin-based mechanism linking RNF2 missense variants to both neurodevelopmental pathology and oncogenic plasticity.","dates":{"publication":"2026/06/22"},"accession":"GSE302414","cross_references":{"GSM":["GSM9103717","GSM9103716","GSM9103719","GSM9103718","GSM9103723","GSM9103720","GSM9103722","GSM9103721"],"GPL":["18573"],"GSE":["302414"],"taxon":["Homo sapiens"]}}