Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis
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.
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Author
Zeller, Peter;
Yeung, JakeISTA 
;
Viñas Gaza, Helena;
de Barbanson, Buys Anton;
Bhardwaj, Vivek;
Florescu, Maria;
van der Linden, Reinier;
van Oudenaarden, Alexander
;
Viñas Gaza, Helena;
de Barbanson, Buys Anton;
Bhardwaj, Vivek;
Florescu, Maria;
van der Linden, Reinier;
van Oudenaarden, AlexanderDepartment
Abstract
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.
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Date Published
2023-02-01
Journal Title
Nature Genetics
Acknowledgement
We thank A. Giladi for sharing mRNA abundance tables of cell types together with J. van den Berg for critical reading of the manuscript. We thank M. Bartosovic for sharing method comparison data. pK19pA-MN was a gift from Ulrich Laemmli (Addgene plasmid 86973, http://n2t.net/addgene:86973; RRID:Addgene_86973). Figure 8 is adopted from Hematopoiesis (human) diagram by A. Rad and M. Häggström under CC-BY-SA 3.0 license. This work was supported by European Research Council Advanced under grant ERC-AdG 742225-IntScOmics and Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP award NWO-CW 714.016.001. The SNF (P2BSP3-174991), HFSP (LT000209/2018-L) and Marie Skłodowska-Curie Actions (798573) supported P.Z. The SNF (P2ELP3_184488) and HFSP (LT000097/2019-L) supported J.Y. and the EMBO LTF (ALTF 1197–2019) supported V.B. This work is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Volume
55
Page
333-345
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Cite this
Zeller P, Yeung J, Viñas Gaza H, et al. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. Nature Genetics. 2023;55:333-345. doi:10.1038/s41588-022-01260-3
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. Nature Genetics. Springer Nature. https://doi.org/10.1038/s41588-022-01260-3
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.” Nature Genetics. Springer Nature, 2023. https://doi.org/10.1038/s41588-022-01260-3.
P. Zeller et al., “Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis,” Nature Genetics, vol. 55. Springer Nature, pp. 333–345, 2023.
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, Peter, et al. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” Nature Genetics, vol. 55, Springer Nature, 2023, pp. 333–45, doi:10.1038/s41588-022-01260-3.
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