X-linked genetic factors regulate hematopoietic stem-cell kinetics in females

Abstract

Abstract X inactivation makes females mosaics for 2 cell populations, usually with an approximate 1:1 distribution. Skewing of this distribution in peripheral blood cells is more common among elderly women.1–3 The depletion of hematopoietic stem cells followed by random differentiation may explain the acquired skewing with age.4 However, an animal model suggests that selection processes based on X-linked genetic factors are involved.5 We studied peripheral blood cells from 71 monozygotic twin pairs aged 73 to 93 years and from 33 centenarians, and we found that with age, 1 of the cell populations becomes predominant for most women. We also observed a strong tendency for the same cell line to become predominant in 2 co-twins. This suggests that X-linked genetic factors influence human hematopoietic stem cell kinetics. The fact that females have 2 cell lines with different potentials could be one of the reasons women live longer than men.