ORGANIZATION OF HAEMOPOIETIC STEM CELLS: THE GENERATION-AGE HYPOTHESIS

Publisher Website
Google Scholar
Abstract
This paper proposes that the previous division history of each stem cell is 1 determinant of the functional organization of the hemopoietic stem cell population. Stem cells from a lineage of stem cells which have generated many stem cells (older stem cells) was used in the aminal to form blood before stem cells which have generated few stem cells (younger stem cells). The stem cell generating capacity of a lineage of stem cells is finite. After a given number of generations a stem cell is lost to the stem cell compartment by forming 2 committed precursors of the cell lines. Its part in blood formation is taken by the next oldest stem cell. This proposal is called the generation-age hypothesis. Experimental evidence in support of the proposal was presented. Older stem cells were stripped away from [mouse] normal bone marrow and 13 day fetal liver with phase-specific drugs and a younger population of stem cells was revealed whose capacity for stem cell generation was 3- to 4-fold greater than that of the average normal, untreated population. Normal stem cells were aged by continuous irradiation and serial retransplantation and their stem cell generative capacity declined 8-fold. The stem cell generative capacity of stem cells in the bloodstream was measured. It was a 1/2-1/4 that of normal bone marrow stem cells and a subpopulation of circulating stem cells was found whose capacity for stem cell generation was 1/8-1/40 that of normal femoral stem cells. This subpopulation was identified by its failure to express the brain-associated antigen which was present on 75% of normal femoral stem cells but was not found on their progeny, the committed precursors of granulocytes.