GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE268nnn/GSE268172/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268172GEOGSEfalseStable maintenance of MERVL-positive embryonic stem cells reveals sustained transcriptional programs and enhancer remodelingMouse 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.2026/05/12GSE268172GSM8287209GSM8287208GSM8287191GSM8287190GSM8287210GSM8287199GSM8287198GSM8287231GSM8287230GSM8287197GSM8287196GSM8287195GSM8287194GSM8287193GSM8287192GSM8287218GSM8287217GSM8287216GSM8287215GSM8287214GSM8287213GSM8287212GSM8287211GSM8287219GSM8287221GSM8287188GSM8287187GSM8287220GSM8287207GSM8287229GSM8287228GSM8287206GSM8287227GSM8287205GSM8287204GSM8287226GSM8287225GSM8287203GSM8287224GSM8287202GSM8287201GSM8287223GSM8287222GSM8287200GSM828718921273268172Mus musculus