Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p.
Mingyi QuXiaojing ZouFang FangShouye WangLei XuQuan ZengZeng FanLin ChenWen YueXiaoyan XieXuetao PeiPublished in: Nature communications (2020)
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.
Keyphrases
- binding protein
- liver injury
- drug induced
- bone marrow
- induced apoptosis
- poor prognosis
- signaling pathway
- pulmonary embolism
- red blood cell
- mesenchymal stem cells
- electronic health record
- liver failure
- genome wide
- intensive care unit
- metabolic syndrome
- big data
- insulin resistance
- oxidative stress
- smooth muscle
- small molecule
- endoplasmic reticulum stress
- amino acid
- skeletal muscle
- long non coding rna
- single cell
- pi k akt
- protein protein