Fig. 1

ATAC-seq maps of hematopoietic cell populations exhibit a high degree of reproducibility between replicates and a tight association of MkPs to HSCs. a Two models of epigenetic regulation of HSC fate. In the “permissive fate” model, CREs of lineage-specific genes of all possible lineage outcomes are in an accessible state (green) in HSCs, keeping genes “primed” for subsequent activation. After lineage commitment occurs towards one fate, the accessibility of primed elements of the alternative fate is restricted by epigenetic remodeling (red). In contrast, the “de novo activation” model posits that CREs of lineage-specific genes are in an inaccessible state (red) in HSCs, keeping genes silenced. Lineage commitment occurs by de novo decondensing of chromatin at the appropriate CRE, allowing for subsequent activation of the differentiation program (green). The CREs of alternative lineage fates remain epigenetically repressed (red). b Schematic diagram of the hematopoietic cells used in this study. Six cell populations were investigated: multipotent HSCs (Hematopoietic stem cells), unilineage MkPs (megakaryocyte progenitors) and EPs (erythroid progenitors), and mature GMs (Granulocyte/Macrophages), B cells, and T cells. c tSNE analysis of the ATAC-seq peaks revealed a high concordance of biological replicates. MkPs clustered close to HSCs, while EPs, GMs, B, and T cells separated across the tSNE plot. d Hierarchical clustering revealed high concordance of cell type-specific replicates. Similar to the tSNE analysis, MkPs clustered closest to HSCs. B and T cells were closely associated to each other but distant to HSCs, while GMs and EPs were contained within their own branches, closer to HSCs