Classical hierarchical model of hematopoiesis illustrating where insights from single-cell studies have challenged 3 key assumptions. The question marks indicate the 3 key assumptions in this model that have been challenged by recent insights from single-cell studies: (1) Mk-E cells are generated by a homogeneous population of multipotent, self-renewing HSCs. (2) The first lineage bifurcation separates progenitors with Mk-E/myeloid from those with lymphoid capacity. (3) Mk and E potentials are closely affiliated through to late stages of hematopoietic development. Myeloid and lymphoid subsets exist but are not shown in this figure. Professional illustration by Patrick Lane, ScEYEnce Studios.