Proliferative capacity of murine hematopoietic stem cells.

Abstract
A decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells occurred. Production of differentiated cell progeny was maintained longer than stem cell self-renewal. In normal animals the capcity for self-renewal was not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appeared to be proliferatively quiescent. After apparent recovery frm the alkylating agent busulfan, the probability of stem cell self-renewal was decreased, there was a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells were proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation and increasing proliferative activity. Cells progress in the continuum in 1 direction and such progression was not reversible.