Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis.

Area of Science:

• Epigenetics
• Developmental Biology
• Hematopoiesis

Background:

• Post-translational histone modifications regulate gene expression by altering chromatin activity.
• Understanding how chromatin states influence single-cell lineage decisions in hematopoiesis is crucial but underexplored.

Purpose of the Study:

• To investigate the role of active and repressive histone modifications in lineage choice during mouse bone marrow hematopoiesis.
• To map dynamic changes in chromatin states during hematopoietic stem and progenitor cell (HSPC) differentiation.

Main Methods:

• Development and application of sort-assisted single-cell chromatin immunocleavage (sortChIC).
• Simultaneous profiling of active (H3K4me1, H3K4me3) and repressive (H3K27me3, H3K9me3) histone marks in single mouse bone marrow cells.
• Chromatin trajectory analysis to model differentiation pathways.

Main Results:

• HSPCs acquire lineage-specific active chromatin states driven by transcription factors during differentiation.
• Alterations in repressive histone marks largely occur independently of the final cell type.
• Lineage commitment at the chromatin level is established at the progenitor stage.
• Myeloid lineage cell types exhibit distinct active chromatin but share common myeloid-specific heterochromatin states.

Conclusions:

• Hematopoiesis involves hierarchical chromatin regulation, with heterochromatin dynamics dictating differentiation trajectories and lineages.
• Euchromatin dynamics, specifically active marks, reflect and define cell types within established lineages.