{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE294nnn/GSE294939/"]},"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=GSE294939"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Decoding Plasticity Regulators and Transition Trajectories in Glioblastoma with Single-cell Multiomics [RNA-seq]","description":"Glioblastoma (GB) is incurable and resistant to therapy despite genomic stability under treatment, implicating non-genetic cellular plasticity as a central driver of progression. Whether such plasticity reflects stochastic state switching or is governed by predictable gene regulation has remained unresolved. We applied scDORI, a deep-learning framework that infers enhancer-driven gene regulatory networks at single cell resolution, to single-nucleus multi-ome profiles of over one million cells from primary GBs. Integrating computational inference with systematic gain-of-function screens across patient-derived models, we show that GB cellular plasticity is governed by a structured regulatory program with an asymmetric interplay of activators and repressors. The resulting transition landscape is hierarchical and predictable, yet permits cross-lineage trajectories absent from normal neurodevelopment. Within this landscape, low-plasticity states such as the Neuronal-like state are not stable differentiation endpoints but actively maintained configurations, stabilized by a network of safeguard repressors that silence alternate fates. MYT1L emerged as the dominant member of this network, binding and repressing master regulators of every alternative state to consolidate Neuronal-like identity. MYT1L restricted plasticity even under standard-of-care therapy and suppressed tumor growth and invasion in vivo. Conversely, MYT1L loss reactivated plasticity and accelerated malignant features, demonstrating that low-plasticity identity requires continuous repression. These findings reframe malignant cell state stability as a balance between activation and continuous repression, and nominate safeguard repressors as candidate therapeutic targets distinct from differentiation-inducing activators, with potential relevance across cancers in which phenotypic switching drives therapy resistance.","dates":{"publication":"2026/08/24"},"accession":"GSE294939","cross_references":{"GSM":["GSM8931692","GSM9832708","GSM8931691","GSM8931690","GSM9832670","GSM9832673","GSM9832630","GSM9832710","GSM9832677","GSM9832632","GSM9832679","GSM9832678","GSM8931699","GSM9832634","GSM8931698","GSM8931697","GSM8931696","GSM9832639","GSM9832638","GSM8931695","GSM8931694","GSM8931693","GSM9832680","GSM9832682","GSM9832681","GSM9832640","GSM8931705","GSM9832683","GSM8931704","GSM9832642","GSM9832685","GSM8931703","GSM8931702","GSM9832688","GSM8931701","GSM9832687","GSM9832643","GSM8931700","GSM9832645","GSM9832689","GSM9832648","GSM9832647","GSM9832691","GSM9832690","GSM9832693","GSM9832695","GSM9832694","GSM9832653","GSM9832652","GSM9832655","GSM9832698","GSM9832657","GSM9832659","GSM9832617","GSM9832616","GSM9832618","GSM9832660","GSM9832662","GSM9832661","GSM9832663","GSM9832621","GSM9832665","GSM9832701","GSM9832668","GSM8931689","GSM9832667","GSM8931688","GSM9832623","GSM9832626","GSM9832625","GSM9832669","GSM9832704","GSM9832627","GSM9832706"],"GPL":["34284","24676"],"GSE":["294939"],"taxon":["Homo sapiens"]}}