Proposed model of heptad activity across hematopoietic differentiation. (A) Heptad TFs form a densely interconnected network, with key regulatory elements accessible and heptad-bound in normal and leukemic stem cells. Accessibility of regulatory elements and, consequently, heptad connectivity are reduced as cells become more differentiated. (B) scRNAseq populations in normal and ME-1 cell populations. GATA2, TAL1, and ERG promote cell state changes along the HSC-ery-precursor axis in both normal CD34⁺ HSPCs and ME-1 cells.