{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE294nnn/GSE294518/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"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=GSE294518"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Decoding Plasticity Regulators and Transition Trajectories in Glioblastoma with Single-cell Multiomics [CUT&RUN]","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":"GSE294518","cross_references":{"GSM":["GSM8908310","GSM8908311","GSM8908312","GSM8908313","GSM8908314","GSM8908315","GSM8908304","GSM8908305","GSM8908306","GSM8908307","GSM8908308","GSM8908309"],"GPL":["30173"],"GSE":["294518"],"taxon":["Homo sapiens"]}}