Rosendaal M, Hodgson G S, Bradley T R
Cell Tissue Kinet. 1979 Jan;12(1):17-29. doi: 10.1111/j.1365-2184.1979.tb00110.x.
This paper proposes that the previous division history of each stem cell is one determinant of the functional organization of the haemopoietic stem cell population. Stem cells from a lineage of stem cells which have generated many stem cells (older stem cells) are used in the animal 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 two committed precursors of the cell lines. Its part in blood formation is taken by the next oldest stem cell. We have called this proposal the generation-age hypothesis. Experimental evidence in support of the proposal is presented. We stripped away older stem cells from normal bone marrow and 13 day foetal liver with phase-specific drugs and revealed a younger population of stem cells whose capacity for stem cell generation was three- to four-fold greater than that of the average normal, untreated population. We aged normal stem cells by continuous irradiation and serial retransplantation and found that their stem cell generative capacity had declined eight-fold. We measured the stem cell generative capacity of stem cells in the bloodstream. It was a half to a quarter that of normal bone marrow stem cells and we found a subpopulation of circulating stem cells whose capacity for stem cell generation was an eighth to a fortieth 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.
本文提出，每个干细胞先前的分裂历史是造血干细胞群体功能组织的一个决定因素。在动物体内，来自产生了许多干细胞的干细胞谱系（较老的干细胞）的干细胞，会先于产生较少干细胞的干细胞谱系（较年轻的干细胞）用于形成血液。干细胞谱系的干细胞生成能力是有限的。经过一定数量的世代后，一个干细胞通过形成细胞系的两个定向祖细胞而从干细胞区室中消失。其在血液形成中的作用由次老的干细胞取代。我们将这一假说称为代龄假说。文中给出了支持该假说的实验证据。我们用阶段特异性药物从正常骨髓和13日龄胎肝中去除较老的干细胞，发现了一个较年轻的干细胞群体，其干细胞生成能力比正常未处理的平均群体高三到四倍。我们通过连续照射和系列再移植使正常干细胞老化，发现它们的干细胞生成能力下降了八倍。我们测量了血流中干细胞的干细胞生成能力。其能力是正常骨髓干细胞的二分之一到四分之一，并且我们发现了一个循环干细胞亚群，其干细胞生成能力是正常股骨干细胞的八分之一到四十分之一。该亚群是通过其不表达脑相关抗原来鉴定的，这种抗原存在于75%的正常股骨干细胞上，但在它们的后代即粒细胞定向祖细胞上未发现。
