Evidence that hematopoiesis may be a stochastic process in vivo
Evidence that hematopoiesis may be a stochastic process in vivo
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DOI：
10.1038/nm0296-190
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发表时间：
1996-02-01
期刊：
影响因子：
82.9
通讯作者：
Guttorp, P
中科院分区：
文献类型：
--
作者：
Abkowitz, JL;Catlin, SN;Guttorp, P
为了研究造血干细胞在体内的行为，通过假设所有干细胞的决定(即复制、凋亡、启动分化/成熟程序)都是偶然的，模拟了造血。模拟实验的预测结果与葡萄糖6-磷酸脱氢酶(G6PD)杂合雌性Safari猫自体骨髓移植研究中获得的数据进行了比较。用这种方法，我们证明了随机分化可以导致体内观察到的广泛的离散结果，并且克隆优势可以偶然发生。由于分析还表明，猫造血干细胞的频率仅为每10(7)个有核骨髓细胞中的6个，并且干细胞复制的平均频率不超过每三周一次，这些大型动物数据对骨髓移植和基因治疗的临床策略提出了挑战。
To study the behavior of hematopoietic stem cells in vivo, hematopoiesis was simulated by assuming that all stem cell decisions (that is, replication, apoptosis, initiation of a differentiation/maturation program) were determined by chance. Predicted outcomes from simulated experiments were compared with data obtained in autologous marrow transplantation studies of glucose 6-phosphate dehydrogenase (G6PD) heterozygous female Safari cats. With this approach, we prove that stochastic differentiation can result in the wide spectrum of discrete outcomes observed in vivo, and that clonal dominance can occur by chance. As the analyses also suggest that the frequency of feline hematopoietic stem cells is only 6 per 10(7) nucleated marrow cells, and that stem cells do not replicate on average more frequently than once every three weeks, these large-animal data challenge clinical strategies for marrow transplantation and gene therapy.