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Stable maintenance of MERVL-positive embryonic stem cells reveals sustained transcriptional programs and enhancer remodeling

GSE268172 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 45 samples Submitted 2026/05/12 Platform GPL21273
Summary
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.
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Direct links to NCBI, no account and no request form: the whole study as GSE268172_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 45 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1114868 and SRA study SRP509310. Searching any of these in the dataset finder brings you back here.

Study design
18 conditions, mostly in duplicate
1-5 red, ZHBTc4-2c-tcTomato-HisD, H3K4me3 ChI… ×2 1-5 red, ZHBTc4-2c-tcTomato-HisD, H3K27ac ChI… ×2 1-9 red, ZHBTc4-2c-tcTomato-HisD, H3K4me3 ChI… ×2 1-9 red, ZHBTc4-2c-tcTomato-HisD, H3K27ac ChI… ×2 2-10 red, ZHBTc4-2c-tcTomato-HisD, H3K4me3 Ch… ×2 2-10 red, ZHBTc4-2c-tcTomato-HisD, H3K27ac Ch… ×2 2-1 mosaic, ZHBTc4-2c-tcTomato-HisD, H3K4me3 … ×2 2-1 mosaic, ZHBTc4-2c-tcTomato-HisD, H3K27ac … ×2 +14 more

Supports a between-group comparison across 36 samples.

18 replicated groups read from the first 40 of 45 sample titles; they account for 36 of them. Check it against the sample list below before relying on it.

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