Estimation of clonal competition intensity in old mice show significantly greater inter-clonal competition but equal growth rates.

A. LSK cell counts for a cohort for 3 month old (n = 5) mice were compared to 11 month old, aged mice (n = 6). There was an 80% decline in LSK numbers (Welch’s unequal variances t-test, p B. In an uncompromised bone marrow system where Δ = 0, this relative decline in HSCs to 20% of their homeostatic numbers (red line, 2000 cells) was extrapolated to a competition coefficient of h1 = h2 = 8.85 (black line). This is in contrast to an expected competition coefficient in healthy HSCs of h1 = h2 = 1. Furthermore, this could be an underestimation since more gated LSK-SLAM populations suggest true HSC declines could be much larger (see Results). C. Competition exacerbates the damaging impacts of bone marrow damage. Importantly, if bone marrow damage is above a certain threshold, Δ ≈ 0.1 day−1 (white dashed line), then the hematopoietic system is driven to extinction regardless of the degree of interclonal competition. However, for situations where the bone marrow damage is not as severe, interclonal competition increases lead to lower total HSC populations. However, when Δ is unknown, as in older mice, this relative decline can be mapped onto a combination of Δ and h values (black dashed line).