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Evidence that hematopoiesis may be a stochastic process in vivo

Nature Medicine volume 2, pages 190197 (1996) | Download Citation

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Abstract

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 107 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.

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Affiliations

  1. Division of Hematology, Department of Medicine, Box 357710, University of Washington, Seattle, Washington 98195, USA

    • Janis L. Abkowitz
  2. Department of Statistics, University of Washington, Seattle, Washington 98195, USA

    • Sandra N. Catlin
    •  & Peter Guttorp

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DOI

https://doi.org/10.1038/nm0296-190

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