(@juliecocquet.bsky.social)

Genome-coverage single-cell histone modifications for embryo lineage tracing | Nature Substantial epigenetic resetting during early embryo development from fertilization to blastocyst formation ensures zygotic genome activation and leads to progressive cellular heterogeneities1–3. Mapping single-cell epigenomic profiles of core histone modifications that cover each individual cell is a fundamental goal in developmental biology. Here we develop target chromatin indexing and tagmentation (TACIT), a method that enabled genome-coverage single-cell profiling of seven histone modifications across mouse early embryos. We integrated these single-cell histone modifications with single-cell RNA sequencing data to chart a single-cell resolution epigenetic landscape. Multimodal chromatin-state annotations showed that the onset of zygotic genome activation at the early two-cell stage already primes heterogeneities in totipotency. We used machine learning to identify totipotency gene regulatory networks, including stage-specific transposable elements and putative transcription factor https://doi.org/10.1038/s41586-025-08656-1