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

Kovtonyuk LV; Manz MG; Takizawa H

doi:10.1182/blood-2015-09-669929

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Journal article

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

Granulocyte Colony-Stimulating Factor

Receptors, Granulocyte Colony-Stimulating Factor

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.

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