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Enhanced thrombopoietin but not G-CSF receptor stimulation induces self-renewing hematopoietic stem cell divisions in vivo.

  • Kovtonyuk LV Division of Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland; and.
  • Manz MG Division of Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland; and.
  • Takizawa H Division of Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland; and International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • 2016-05-06
Published in:
  • Blood. - 2016
Animals
Cell Division
Cells, Cultured
Granulocyte Colony-Stimulating Factor
Hematopoiesis
Hematopoietic Stem Cells
Heterocyclic Compounds
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Fc
Receptors, Granulocyte Colony-Stimulating Factor
Receptors, Thrombopoietin
Recombinant Fusion Proteins
Thrombopoietin
English In steady-state adult hematopoiesis, most hematopoietic stem cells (HSCs) are in the resting phase of the cell cycle. Upon enhanced hematopoietic demand, HSCs can be induced to divide and self-renew or differentiate. However, the cell-extrinsic signals inducing HSC cycling remain to be elucidated. Using in vivo high-resolution single HSC divisional tracking, we directly demonstrate that clinically applied thrombopoietin receptor but not granulocyte colony-stimulating factor (G-CSF) receptor agonists drive HSCs into self-renewing divisions leading to quantitative expansion of functional HSC as defined by their in vivo serial multilineage and long-term repopulating potential. These results suggest that thrombopoietin mimetics might be applicable to expand HSCs in vivo and to sensitize thrombopoietin receptor-expressing HSCs to cell cycle-dependent cytotoxic agents.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/236003
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