Estimating Dormant and Active Hematopoietic Stem Cell Kinetics through Extensive Modeling of Bromodeoxyuridine Label-Retaining Cell Dynamics
Figure 3
Deterministic LRC model predictions of BrdU content.
Brown line: HSC chase; red line: d-HSC; green line: a-HSC; dashed line: HSC uptake; blue x: observed data. Left panel: stage 1 & 2 predictions (uptake and first 10 days of chase) on a timescale of hours; right panel: uptake and chase predictions on a timescale of days. (A) One-population model predictions. This model can satisfactorily describe BrdU uptake but not the long term label-retention. (B) Two-population model predictions with a BDT of 4 and 30% d-HSC proportion. The effect of a smaller d-HSC population is visible in the left panel of this plot. (C) Two-population model predictions with a BDT of 6 or 7 and 40% d-HSC proportion. This model gave the best overall goodness-of-fit. Activation of the d-HSCs can be clearly seen in the left panel where both d-HSC and a-HSC are predicted to take BrdU up at the same rate (cycling about once every 10 days). During chase d-HSCs return to a dormant state and are predicted to divide about once every 165 days, whilst a-HSCs divide once every 31 days, diluting label much faster than the d-HSCs.