EVIDENCE FOR THE MAINTENANCE OF HEMATOPOIESIS IN A LARGE ANIMAL BY THE SEQUENTIAL ACTIVATION OF STEM-CELL CLONES
EVIDENCE FOR THE MAINTENANCE OF HEMATOPOIESIS IN A LARGE ANIMAL BY THE SEQUENTIAL ACTIVATION OF STEM-CELL CLONES
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DOI：
10.1073/pnas.87.22.9062
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发表时间：
1990-11-01
影响因子：
11.1
通讯作者：
GUTTORP, P
中科院分区：
文献类型：
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作者：
ABKOWITZ, JL;LINENBERGER, ML;GUTTORP, P
为了测试造血是否可以通过连续激活干细胞克隆来维持，我们在X染色体连锁酶葡萄糖-6磷酸脱氢酶（G6 PG）杂合子的猫中进行了有限数量细胞的自体骨髓移植，并观察了红细胞和粒细胞/巨噬细胞祖细胞随时间的G6 PD表型。这些动物是Geoffroy公猫和家猫的雌性后代。在对对照动物（n = 5）或移植前实验动物（n = 3）的骨髓进行的重复研究中，具有国产型G6 PD的祖细胞的百分比没有变化。移植后，外周血细胞计数、骨髓形态、祖细胞频率和祖细胞周期动力学恢复正常。然而，在1-1.5年的观察期间，在每只猫的G6 PD型祖细胞中观察到突然和显著的波动。这些数据不能解释，如果有一个大的或恒定的人口活跃的干细胞，从而意味着，在大型动物系统中，造血是通过克隆演替维持。建立了一个随机模型来估计活性克隆的数量和它们的平均寿命。
To test if hematopoiesis can be maintained by the sequential activation of stem-cell clones, we performed autologous marrow transplantations with limited numbers of cells in cats heterozygous for the X-chromosome-linked enzyme glucose-6 phosphate dehydrogenase (G6PG) and observed the G6PD phenotypes of erythroid and granulocyte/macrophage progenitors over time. The animals were the female offspring of Geoffroy male and domestic female cats. In repeated studies of marrow from control animals (n = 5) or experimental animals prior to transplantation (n = 3), the percent of progenitors with domestic-type G6PD did not vary. After transplantation, the peripheral blood counts, marrow morphologies, frequencies of progenitors,and progenitor cell cycle kinetics returned to normal. However, abrupt and significant fluctuations were seen in the G6PD type of progenitors from each cat during the 1-1.5 years of observation. These data cannot be explained if there were either a large or constant population of active stem cells and thus imply, in large-animal system, that hematopoiesis was maintined through clonal succession. A stochastic model was developed to estimate the numbers of active clones and their mean lifetimes.