Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p

Mingyi Qu, Xiaojing Zou, Fang Fang, Shouye Wang, Lei Xu, Quan Zeng, Zeng Fan, Lin Chen, Wen Yue, Xiaoyan Xie () and Xuetao Pei ()
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Mingyi Qu: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Xiaojing Zou: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Fang Fang: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Shouye Wang: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Lei Xu: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Quan Zeng: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Zeng Fan: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Lin Chen: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Wen Yue: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Xiaoyan Xie: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing
Xuetao Pei: Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.

Date: 2020
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DOI: 10.1038/s41467-020-18802-0

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