Hematopoiesis as a competitive exclusion process: Estimation of a stem cell selective advantage

The replication rate of human hematopoietic stem cells in vivo

“…Our data indicate that human HSCs replicate on average once per 40 weeks (range, 25-50 weeks) and, therefore, slower than nonhuman primate HSCs (ϳ once per 25 weeks) 47 and much slower than cat (ϳ once per 8.3 weeks) 7,8 or mouse (ϳ once per 2.5 weeks) 6 HSCs, when studied with comparable methods.…”

“…36,37 A limited replication capacity and mandatory senescence would help preserve genetic integrity. An HSC in Safari cats replicates approximately once every 8.3 weeks, 7,8 resulting in 94.0 replications during an average cat life span of 15 years. 39 In C57BL/6J mice, HSCs replicate approximately once every 2.5 weeks, 16,26,27 resulting in 58.9 HSC replications per average life span of 34.3 months.…”

“…Using the description of hematopoiesis in Figure 1 and the value of derived from competitive transplantation studies (once per 8.3 weeks), we estimated that a 5% replication advantage for HSCs expressing X-chromosome alleles from the Geoffroy (vs domestic) parent would be sufficient to lead to the hemizygous selection of Geoffroy-type HSCs and explain these data. 8 To analyze human hematopoiesis, we reasoned that X-chromosome polymorphisms in the outbred human population (only ϳ 150 000 years of genetic distance and chromosomal divergence 18 ) would provide the same or fewer differences among HSC replication rates. With this single constraint, we analyzed data from Busque (Montreal cohort), which consists of 1219 observations in females 18 to 100 years of age (mean, 55.9 Ϯ 22.0 years).…”

“…They are amenable to describing how HSCs support hematopoiesis and specifically to defining the average rate, , at which HSCs replicate in vivo ( Figure 1). By analyzing competitive transplantation studies, [6][7][8] we have previously estimated for mouse and cat HSCs as once per 2.5 weeks and 8.3 weeks, respectively. Here, we apply similar stochastic methods to analyze the changing ratio of maternal/paternal X-chromosome phenotypes in blood cells of 1219 females 18 to 100 years of age (Montreal cohort) and 117 females 18 to 96 years of age (London cohort) to derive for human hematopoiesis.…”

Estimating human hematopoietic stem cell kinetics using granulocyte telomere lengths

“…The model makes the assumption (A5) that the maximum number of HSC at any given time is K (representing a full niche) [32]. If there is a replication and there are already K stem cells then one stem cell dies.…”