Evidence that hematopoiesis may be a stochastic process in vivo.
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 sem 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.
Abkowitz
J L
JL
Department of Medicine, University of Washington, Seattle 98195, USA.
Catlin
S N
SN
Guttorp
P
P
D000818:Animals; D016026:Bone Marrow Transplantation; D002415:Cats; D002454:Cell Differentiation; D002455:Cell Division; D003198:Computer Simulation; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology*; D008390:Markov Chains