Unipotent Megakaryopoietic Pathway Bridging Hematopoietic Stem Cells and Mature Megakaryocytes

Stem Cells
Hidekazu NishikiiShigeru Chiba

Abstract

Recent identification of platelet/megakaryocyte-biased hematopoietic stem/repopulating cells requires revision of the intermediate pathway for megakaryopoiesis. Here, we show a unipotent megakaryopoietic pathway bypassing the bipotent megakaryocyte/erythroid progenitors (biEMPs). Cells purified from mouse bone marrow by CD42b (GPIbα) marking were demonstrated to be unipotent megakaryocytic progenitors (MKPs) by culture and transplantation. A subpopulation of freshly isolated CD41(+) cells in the lineage Sca1(+) cKit(+) (LSK) fraction (subCD41(+) LSK) differentiated only into MKP and mature megakaryocytes in culture. Although CD41(+) LSK cells as a whole were capable of differentiating into all myeloid and lymphoid cells in vivo, they produced unipotent MKP, mature megakaryocytes, and platelets in vitro and in vivo much more efficiently than Flt3(+) CD41(-) LSK cells, especially at the early phase after transplantation. In single cell polymerase chain reaction and thrombopoietin (TPO) signaling analyses, the MKP and a fraction of CD41(+) LSK, but not the biEMP, showed the similarities in mRNA expression profile and visible TPO-mediated phosphorylation. On increased demand of platelet production after 5-FU treatment, a part of CD...Continue Reading

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Citations

Jan 21, 2016·Blood·Koji Eto, Shinji Kunishima
Jan 21, 2016·Blood·Carolien M Woolthuis, Christopher Y Park
Nov 12, 2015·BioMed Research International·Ondrej Svoboda, Petr Bartunek
May 10, 2017·Nature Communications·Antonio PieriniRobert S Negrin
Jul 7, 2017·Stem Cells Translational Medicine·Hidekazu NishikiiShigeru Chiba
May 29, 2018·Blood·Shilei ChenJunping Wang
Oct 7, 2018·The Journal of Experimental Medicine·Samik UpadhayaBoris Reizis
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May 28, 2019·Thrombosis Research·Genevieve Couldwell, Kellie R Machlus

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