Presentation Information
[C14-05]Simulation of hematopoietic stem cell diversity
*Koichi Saeki1, Hiroshi Haeno1 (1. Tokyo University of Science (Japan))
Keywords:
hematopoietic stem cells,Moran process
In the aging process, hematopoietic stem cells (HSCs) are subject to somatic mutations and few of them may increase the selective growth advantage of the cell in which it occurs. This may lead the overrepresentation of blood cells derived from a single clone, which is called clonal hematopoiesis. Clonal hematopoiesis attracts a great deal of attention because it is associated with not only the risk of developing blood cancers but also the risk of cardiovascular diseases. Recently, the whole-genome sequencing of single-cell-derived colonies of HSCs revealed that the clonal diversity of HSC population in individuals aged > 75 decreas rapidly. However, the obsevation is based a limited number of HSCs and how much this result reflects the dynamics of whole HSC population is unclear.
Here we adopted Moran process to 105 of HSC population and traced the timecource of the clonal diversity of the whole HSC population. In this model, when a cell obtains a advantagerous mutation during a cell division, the fitness of the cell additively increases and it is likely to be selected as a dividing cell. Our results suggests that the rapid decline of clonal diversity in elderly people is due to both the effect of advantagerous mutations and small cell number to calculate the clonal diversity. Moreover, we’d like to discuss the effect of disturbance on the populattion and its detectability frrom the limited number of sampled cells.
Here we adopted Moran process to 105 of HSC population and traced the timecource of the clonal diversity of the whole HSC population. In this model, when a cell obtains a advantagerous mutation during a cell division, the fitness of the cell additively increases and it is likely to be selected as a dividing cell. Our results suggests that the rapid decline of clonal diversity in elderly people is due to both the effect of advantagerous mutations and small cell number to calculate the clonal diversity. Moreover, we’d like to discuss the effect of disturbance on the populattion and its detectability frrom the limited number of sampled cells.