article published yes Peter Zeller author Jake Yeung author 123012b2-db30-11eb-b4d8-a35840c0551b0000-0003-1732-1559 Helena Viñas Gaza author Buys Anton de Barbanson author Vivek Bhardwaj author Maria Florescu author Reinier van der Linden author Alexander van Oudenaarden author ScienComp department Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages. https://research-explorer.ista.ac.at/download/12158/12688/2023_NatureGenetics_Zeller.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Springer Nature2023 eng Genetics 1061-4036 1546-1718 3653961710.1038/s41588-022-01260-3 55333-345 Zeller P, Yeung J, Viñas Gaza H, et al. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. 2023;55:333-345. doi:<a href="https://doi.org/10.1038/s41588-022-01260-3">10.1038/s41588-022-01260-3</a> P. Zeller, J. Yeung, H. Viñas Gaza, B.A. de Barbanson, V. Bhardwaj, M. Florescu, R. van der Linden, A. van Oudenaarden, Nature Genetics 55 (2023) 333–345. Zeller P, Yeung J, Viñas Gaza H, de Barbanson BA, Bhardwaj V, Florescu M, van der Linden R, van Oudenaarden A. 2023. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. Nature Genetics. 55, 333–345. Zeller, P., Yeung, J., Viñas Gaza, H., de Barbanson, B. A., Bhardwaj, V., Florescu, M., … van Oudenaarden, A. (2023). Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41588-022-01260-3">https://doi.org/10.1038/s41588-022-01260-3</a> Zeller, Peter, Jake Yeung, Helena Viñas Gaza, Buys Anton de Barbanson, Vivek Bhardwaj, Maria Florescu, Reinier van der Linden, and Alexander van Oudenaarden. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” <i>Nature Genetics</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41588-022-01260-3">https://doi.org/10.1038/s41588-022-01260-3</a>. Zeller, Peter, et al. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” <i>Nature Genetics</i>, vol. 55, Springer Nature, 2023, pp. 333–45, doi:<a href="https://doi.org/10.1038/s41588-022-01260-3">10.1038/s41588-022-01260-3</a>. P. Zeller <i>et al.</i>, “Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis,” <i>Nature Genetics</i>, vol. 55. Springer Nature, pp. 333–345, 2023. 121582023-01-12T12:09:09Z2025-04-23T08:45:00Z