Ayako Nakamura-Ishizu
   Department   School of Medicine, School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title Thrombopoietin maintains cell numbers of hematopoietic stem and progenitor cells with megakaryopoietic potential.
Journal Formal name:Haematologica
Abbreviation:Haematologica
ISSN code:15928721/03906078
Domestic / ForeginForegin
Volume, Issue, Page Jun 11(haematol.2019.241406),pp.000-000
Author and coauthor O'Neill Aled, Chin Desmond, Tan Darren, Abdul Majeed A Qilah Banu Bte, Nakamura-Ishizu Ayako, Suda Toshio
Publication date 2020/06
Summary Thrombopoietin (THPO) has long been known to influence megakaryopoiesis and hematopoietic stem and progenitor cells (HSPCs), though the exact mechanisms through which it acts are unknown. Here we show that MPL expression correlates with megakaryopoietic potential of HSPCs and identify a population of quiescent progenitor cells that show limited dependence on THPO signalling. We show that THPO is primarily responsible for maintenance of hematopoietic cells with megakaryocytic (Mk) differentiation potential and their subsequent Mk differentiation and maturation. The loss of Mks in THPO knockout (KO) mouse models results in a reduction of the Mk derived chemokine platelet factor 4 (CXCL4/PF4) in the bone marrow and administration of recombinant CXCL4/PF4 rescues the loss of progenitor cell quiescence observed in these mice. CXCL4/PF4 treatment does not rescue reduced HSPC numbers suggesting that thrombopoietin directly maintains HSPC numbers.
DOI 10.3324/haematol.2019.241406
PMID 32527954