{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320141/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320141"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Stable maintenance of MERVL-positive embryonic stem cells reveals sustained transcriptional programs and enhancer remodeling [scRNA-seq]","description":"Mouse embryonic stem cells (ESCs) occasionally transit into a rare two-cell-like (2C) state characterized by transient activation of endogenous retroviruses such as MERVL and expression of 2C-specific genes including the Zscan4 cluster. These 2C-like cells (2CLCs) resemble early blastomeres and display expanded developmental potential, but their unstable and sporadic nature has hindered mechanistic studies. Here, we demonstrate the transiently stable maintenance of MERVL-positive ESCs that exhibit persistent MERVL expression and activation of 2C-associated genes. Live-cell imaging revealed uniform and sustained MERVL activity in these MERVL-positive ESCs, contrasting with the heterogeneous and transient expression observed in conventional ESCs. Transcriptome profiling demonstrated robust induction of 2C-specific regulatory networks, and embryoid body differentiation combined with machine learning uncovered increased lineage variability and altered developmental trajectories. Single-cell RNA sequencing revealed clear separation of control ESCs from MERVL-positive populations and redistribution across distinct transcriptional states, with Red and Mosaic lines showing graded shifts within a shared transcriptional manifold. Epigenomic profiling further revealed distinct chromatin states, specialized super-enhancer landscapes, and active enhancer marking at MERVL loci. Together, these findings demonstrate that stable maintenance of MERVL-positive ESCs is achievable in vitro, providing a powerful model to dissect ERV-driven transcriptional regulation, epigenomic remodeling, and 2C-like transcriptional and epigenetic programs.","dates":{"publication":"2026/05/12"},"accession":"GSE320141","cross_references":{"GSM":["GSM9535603"],"GPL":["19057"],"GSE":["320141"],"taxon":["Mus musculus"]}}