Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis

Peter Zeller, Jake Yeung, Helena Viñas Gaza, Buys Anton de Barbanson, Vivek Bhardwaj, Maria Florescu, Reinier van der Linden, Alexander van Oudenaarden

Research output: Contribution to journal/periodicalArticleScientificpeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)333-345
Number of pages13
JournalNature Genetics
Issue number2
Publication statusPublished - Feb 2023


  • Mice
  • Animals
  • Chromatin/genetics
  • Heterochromatin/genetics
  • Cell Lineage/genetics
  • Epigenesis, Genetic
  • Hematopoiesis/genetics
  • Cell Differentiation/genetics


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