Mehr R, Abel L, Ubezio P, Globerson A, Agur Z
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Mech Ageing Dev. 1993 Feb;67(1-2):159-72. doi: 10.1016/0047-6374(93)90120-g.
The process of T cell generation in the thymus involves complex cell-cell interactions between the various types of thymic stromal cells, thymocyte progenitors, thymocytes at different stages of differentiation and external factors. We applied the tool of mathematical modelling to analyze hypotheses and direct experiments concerning mechanisms underlying the observed developmental inferiority of bone-marrow thymocyte progenitors from old mice. Previous experimental data showed that lower cell numbers were obtained from old bone marrow-derived thymocyte progenitors, compared to young bone marrow-derived progenitors, when colonizing simultaneously the same fetal thymus. In this study, simulations based on the mathematical model indicate that the developmental inferiority of old bone marrow-derived progenitors cannot be explained by a change in a single parameter, such as the observed differences in progenitor frequency, an increase in cell cycle duration, a reduction in the fraction of proliferating cells in old age, and/or an increase in the rate of cell death. We have performed experimental measurements of the fractions of cycling cells. No significant difference was found between these fractions in young and old bone marrow-derived thymocytes. The difference in developmental patterns of young and old bone marrow-derived thymocytes may be due to a combination of more than one mechanism, possibly including interactions between competing thymocytes of old and young bone marrow origin.
胸腺中T细胞的生成过程涉及多种类型的胸腺基质细胞、胸腺细胞祖细胞、不同分化阶段的胸腺细胞以及外部因素之间复杂的细胞间相互作用。我们应用数学建模工具来分析关于老年小鼠骨髓胸腺细胞祖细胞发育劣势潜在机制的假设并指导实验。先前的实验数据表明，当同时定植于同一胎儿胸腺时，与年轻骨髓来源的祖细胞相比，老年骨髓来源的胸腺细胞祖细胞产生的细胞数量更少。在本研究中，基于数学模型的模拟表明，老年骨髓来源祖细胞的发育劣势不能用单一参数的变化来解释，例如观察到的祖细胞频率差异、细胞周期持续时间增加、老年期增殖细胞比例降低和/或细胞死亡率增加。我们已经对循环细胞的比例进行了实验测量。在年轻和老年骨髓来源的胸腺细胞中，这些比例没有发现显著差异。年轻和老年骨髓来源的胸腺细胞发育模式的差异可能是由于多种机制的组合，可能包括老年和年轻骨髓来源的竞争性胸腺细胞之间的相互作用。
