ArticleStem cell reports2026
Single cell CRISPR screen identifies antagonism between Nsd1-H3K36me2 and Ezh2-H3K27me3 orchestrates pluripotency transition.
Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The transcriptional and epigenetic landscape imposes constraints on the self-renewal capacity and lineage specification potential of both naive and primed mouse embryonic stem cells (mESCs). CRISPR/Cas9-based functional screening coupled with single-cell RNA-seq (CROP-seq) establishes relationships between gRNA-mediated knockout genotype and transcriptome phenotype, providing a powerful tool to dissect gene regulatory networks. Here, we employed CROP-seq to investigate the epigenetic regulation governing the pluripotency network in mESCs. This highly sensitive method identified key genes essential for the acquisition and exit from pluripotency, and revealed a novel role for H3K36me2 in modulating DNA methylation through regulating the expression of Dnmt1 and Dnmt3a. Specifically, loss of Nsd1-mediated H3K36me2 delayed naive state exit, whereas Ezh2 deficiency accelerated primed entry. Collectively, our findings identify an epigenetic regulatory network critical for determining mESCs' pluripotent state transitions.
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