Chromatin Accessibility Maps Provide Evidence of Multilineage Gene Priming in Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) have the capacity to differentiate into vastly different types of mature blood cells. The epigenetic mechanisms regulating the multilineage ability, or multipotency of HSCs are not well understood. To test the hypothesis that cis regulatory elements that control fate decisions for all lineages are primed in HSCs, we used ATAC-seq to compare chromatin accessibility of HSCs with five unipotent cell types. We observed the highest similarity in accessibility profiles between Megakaryocyte Progenitors and HSCs, whereas B cells had the greatest number of regions with de novo gain in accessibility during differentiation. Despite these differences, we identified cis regulatory elements from all lineages that displayed epigenetic priming in HSCs. These findings provide new insights into the regulation of stem cell multipotency, as well as a resource to identify functional drivers of lineage fate. HIGHLIGHTSO_LIHSCs have higher global chromatin accessibility than any unilineage progeny C_LIO_LIMegakaryocyte Progenitors are the most closely related unipotent cell type to HSCs C_LIO_LIB cell commitment involves de novo chromatin accessibility C_LIO_LIEvidence of cis element priming of lineage-specific genes in HSCs C_LI