The level of c-kit expression predicts the activity of murine hematopoietic stem cells

Abstract

Although c-kit expression on the murine hematopoieticstem cells (HSCs) is essential for the survival of HSCs and maintenance of hematopoiesis, the significance of the high level of expression of c-kit on HSCs has not been well determined. We show here that the intensity of c-kit expression correlates with the cycling status of the population. The HSCs expressinga lower level of c-kit on the cell surface also possess the lower level inside the cells, which cannot be explained by ligand receptor binding and internalization. And therefore it is assumed that the c-kit highly and modestly expressing HSCs are qualitatively different. In accordance with this, HSCs with low c-kit expression have higher p21

and p57 mRNA concentration and are slow to respond to cytokine stimulation. Despite the functional differences in the two populations, both HSCs are uniformly hypoxic and modestly accessible to blood perfusion.Therefore it is suggested that the two population reside in a similar niche environment.The cell fraction with very weak expression of c-kit obtains the ability to long-term reconstitute hematopoiesis, and to generate HSC population with high expression of c-kit, when transplanted in irradiated recipients.