Ema Hideo, Uchinomiya Kouki, Morita Yohei, Suda Toshio, Iwasa Yoh
Department of Cell Differentiation, Sakaguchi Laboratories of Developmental Biology, Keio University School of Medicine, Japan.
Department of Biology, Faculty of Sciences, Kyushu University, Japan.
J Theor Biol. 2016 Apr 7;394:57-67. doi: 10.1016/j.jtbi.2016.01.010. Epub 2016 Jan 20.
The transplantation of blood tissues from bone marrow into a lethally irradiated animal is an experimental procedure that is used to study how the blood system is reconstituted by haematopoietic stem cells (HSC). In a competitive repopulation experiment, a lethally irradiated mouse was transplanted with a single HSC as a test cell together with a number of bone marrow cells as competitor cells, and the fraction of the test cell progeny (percentage of chimerism) was traced over time. In this paper, we studied the stem cell kinetics in this experimental procedure. The balance between symmetric self-renewal and differentiation divisions in HSC determined the number of cells which HSC produce and the length of time for which HSC live after transplantation. The percentage of chimerism depended on the type of test cell (long-, intermediate-, or short-term HSC), as well as the type and number of HSC included in competitor cells. We next examined two alternative HSC differentiation models, one-step and multi-step differentiation models. Although these models differed in blood cell production, the percentage of chimerism appeared very similar. We also estimated the numbers of different types of HSC in competitor cells. Based on these results, we concluded that the experimental results inevitably include stochasticity with regard to the number and the type of HSC in competitor cells, and that, in order to detect different types of HSC, an appropriate number of competitor cells needs to be used in transplantation experiments.
将骨髓中的血液组织移植到经过致死剂量照射的动物体内，是一种用于研究造血干细胞（HSC）如何重建血液系统的实验方法。在竞争性再增殖实验中，将一只经过致死剂量照射的小鼠移植单个HSC作为测试细胞，同时移植若干骨髓细胞作为竞争细胞，并随着时间追踪测试细胞后代的比例（嵌合率百分比）。在本文中，我们研究了该实验方法中的干细胞动力学。HSC对称自我更新与分化分裂之间的平衡，决定了HSC产生的细胞数量以及移植后HSC存活的时间长度。嵌合率百分比取决于测试细胞的类型（长期、中期或短期HSC），以及竞争细胞中所含HSC的类型和数量。接下来，我们研究了两种替代性的HSC分化模型，即一步分化模型和多步分化模型。尽管这些模型在血细胞产生方面存在差异，但嵌合率百分比看起来非常相似。我们还估算了竞争细胞中不同类型HSC的数量。基于这些结果，我们得出结论，实验结果不可避免地在竞争细胞中HSC的数量和类型方面包含随机性，并且为了检测不同类型的HSC，在移植实验中需要使用适当数量的竞争细胞。
