Journal
BLOOD
Volume 127, Issue 25, Pages 3175-3179Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2015-09-669929
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Funding
- Forschungskredit of the University of Zurich
- Japanese Society for the Promotion of Science [15H01519]
- Swiss National Science Foundation [310030_146528]
- Promedica Foundation (Chur, Switzerland)
- Grants-in-Aid for Scientific Research [15H01519] Funding Source: KAKEN
- Swiss National Science Foundation (SNF) [310030_146528] Funding Source: Swiss National Science Foundation (SNF)
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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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