Evidence that hematopoiesis may be a stochastic process in vivo

被引：198

作者：

Abkowitz, JL ^{[1
]}

Catlin, SN ^{[1
]}

Guttorp, P ^{[1
]}

机构：

[1] UNIV WASHINGTON, DEPT STAT, SEATTLE, WA 98195 USA

来源：

NATURE MEDICINE | 1996年 / 2卷 / 02期

关键词：

D O I：

10.1038/nm0296-190

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：190 / 197

页数：8

共 52 条

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