June 24 2016
Kovtonyuk LV, Markus G. Manz, Takizawa H.
Enhanced thrombopoietin but not G-CSF receptor stimulation induces self-renewing hematopoietic stem cell divisions in vivo.
Blood 2016 127:3175-3179; doi:10.1182/blood-2015-09-669929
Thrombopoietin receptor agnoist but not G-CSF induces self-renewing HSC divisions and expansion.
In steady-state adult hematopoiesis, most hematopoietic stem cells (HSCs) are in G0 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 here directly demonstrate that clinically applied thrombopoietin receptor but not granulocyte-colony stimulating factor receptor agonists drive HSCs into self-renewing divisions leading to quantitative expansion of functional HSC as defined by their in vivo serial multi-lineage and long-term repopulating potential. These results suggest that thrombopoietin mimetics might be applicable to expand HSCs in vivo, and furthermore, to sensitize thrombopoietin receptor-expressing HSCs to cell cycle-dependent cytotoxic agents.