Figure 5. Model of mixed-lineage transition states underlying myeloid cell-fate determination.

Model depicts a hierarchical set of hematopoietic intermediates culminating in the specification of monocytic and granulocytic lineages. Cells are ordered on a Waddington landscape with their characteristic gene expression modules (color bars) and states. The prevalent (Multi-Lin*) and rare (bistable) mixed-lineage myeloid transition states, characterized herein, are proposed to manifest dynamic instability because of counteracting regulatory determinants. Although erythroid and megakaryocytic progenitors were found within CMPs, it remains to be determined if a distinct set of Multi-Lin* intermediates give rise to these progenitors via a rare bistable state.