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1.
Fig. 4.

Fig. 4. From: Predicting clonal self-renewal and extinction of hematopoietic stem cells.

A priori prediction of the life span of 27 HSC clones. The predicted (red) and actual (blue) life spans are shown (from Table S3). Axis units are months.

Hans B. Sieburg, et al. Proc Natl Acad Sci U S A. 2011 March 15;108(11):4370-4375.
2.
Fig. 5.

Fig. 5. From: Predicting clonal self-renewal and extinction of hematopoietic stem cells.

Simulating clonal HSC life spans. Two cell types are considered. HSCs can self-renew, be in a quiescent state (G0), or differentiate into precursors and mature cells (DIF). In the simulator, the resting state is a by-product of asynchronous updating (39). The likelihood that a HSC divides into two daughter HSCs or into two DIF cells is determined by transition probabilities. Asymmetrical division scenarios were also considered and gave comparable results.

Hans B. Sieburg, et al. Proc Natl Acad Sci U S A. 2011 March 15;108(11):4370-4375.
3.
Fig. 6.

Fig. 6. From: Predicting clonal self-renewal and extinction of hematopoietic stem cells.

Simulations predict a logistic decline of self-renewal during the life span of HSC clones. (A–H) The simulated %DT (blue) after transplantation of a single HSC. All simulations were extended to 1,600 time points. (Insets) At the level of individual cells, the intrinsic fate probabilities as functions of division history (θ, horizontal axis) that yielded the blue curves. Red, probability of self-renewal (psn); green, probability of differentiation (pdiff). (A and B) Constant psn and pdiff; (C) psn and pdiff decline/increase linearly; (D) psn and pdiff decline/increase elliptically; (E) logistic change of psn and pdiff; (F) logistic psn with constant pdiff; (G) constant psn and increasing pdiff; (H) HSCs with high initial pdiff and low psn.

Hans B. Sieburg, et al. Proc Natl Acad Sci U S A. 2011 March 15;108(11):4370-4375.
4.
Fig. 2.

Fig. 2. From: Predicting clonal self-renewal and extinction of hematopoietic stem cells.

Concerted repopulation kinetics of daughter HSCs within a clone. (A–D) The %DT for individual hosts at different times (horizontal axis) after transplant of single HSCs. (A–C) At the indicated time points, 5 × 106 BM cells from the primary host (x) were transplanted into 2–3 secondary (○) hosts, and then into 4 different tertiary (△) hosts. Occasionally, the symmetry of repopulation levels is broken. For example, one mouse in B rapidly lost DT cells in blood at 18 mo after injection. This mouse died shortly thereafter, suggesting that the abrupt shift in %DT was pathological. (D) A total of 4 × 104 BM cells from the primary host were transferred into 15 secondary mice.

Hans B. Sieburg, et al. Proc Natl Acad Sci U S A. 2011 March 15;108(11):4370-4375.
5.
Fig. 1.

Fig. 1. From: Predicting clonal self-renewal and extinction of hematopoietic stem cells.

Individual HSCs have distinct clonal life spans. (A–L) The %DT at different times after transplant of a single HSC. (A–F) Serial transplants were performed. At the indicated time points HSCs from the primary host (x) were transplanted into the secondary (○), and then the tertiary (△), and finally the quaternary (◆). Because secondary and higher transplants used several hosts per HSC clone, mean repopulation (±SD) is shown. In some instances the errors are too small to be discernible. The small errors reflect the similarities in repopulation kinetics of HSCs within a clone. Extrapolation of the curves to the right intersection with the time axis was used to estimate ”actual” life spans. Early data points for the HSC clones in A and B were published previously (10). (G–L) Clonal HSC life spans without serial transplants. These HSCs aged in the primary host.

Hans B. Sieburg, et al. Proc Natl Acad Sci U S A. 2011 March 15;108(11):4370-4375.
6.
Fig. 3.

Fig. 3. From: Predicting clonal self-renewal and extinction of hematopoietic stem cells.

Ballistic model of clonal aging. (A) Examples of how the function D(t) is derived from the interplay between the growth function D+(t) = bt and the decline function D(t) = −atα. Here, b was fixed and a was normalized to 1. Different values for α yield distinct life-span curves; e.g., for α = 1.6, the decline function (●) interacted with the growth function (▲) to generate a long life span (x). For α = 2.0 (decline function ○), we obtained a short life span (◇). (B) Parameter space of the prediction model. We tested 107 variations of the parameters (b, a, α) by Monte Carlo simulation. For a and b we used a range of 1–105 and 1 < α < 10 [α > 1 excludes linear D(t); α < 10, because large α quickly yields very short life spans (<1 mo)]. Shown are (b, a, α) that generate permissible configurations (1 < T < 1,000). (C) Frequency distribution of α: No permissible values were found for α > 3.52. (D) The shapes of the predicted (○) and the experimental data (x) match well.

Hans B. Sieburg, et al. Proc Natl Acad Sci U S A. 2011 March 15;108(11):4370-4375.

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