A five state model framework for HSC lineage specification.

(A) A schematic of the classical HSC differentiation hierarchy where long-term progenitors (LT-HSC) differentiate into short-term (ST-HSC) progenitors, then multipotent (MPP), then common myeloid progenitors (CMP) before maturing into fully developed myeloid cells (Terminal). (B) A 5-state computational model featuring the LT-HSC, ST-HSC, MPP, CMP, and Terminal cell types. Culture dynamics may be influenced via feedback from cell-secreted biomolecules that stimulate and/or inhibit the proliferation and differentiation rates of each cell type. Additionally, a fraction of ST-HSCs and MPPs would be available to transition directly into Terminal cells without going through CMP differentiation (‘jump’). (C-G) The model simulation is able to capture the dynamics and scale of the experimental data for all 5 cell profiles (C: LT-HSC; D: ST-HSC; E: MPP; F: CMP; G: Terminal) over a 9 day period. Error bars represent standard deviation.