GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE268nnn/GSE268173/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268173GEOGSEfalseStable 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.2026/05/12GSE268173GSM8287254GSM8287243GSM8287232GSM8287253GSM8287242GSM8287241GSM8287252GSM8287251GSM8287240GSM8287250GSM8287239GSM8287238GSM8287249GSM8287248GSM8287237GSM8287247GSM8287236GSM8287246GSM8287235GSM8287245GSM8287234GSM8287244GSM8287255GSM828723321273268173Mus musculus