Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p
| Autor: | Shouye Wang, Zeng Fan, Xiaojing Zou, Wen Yue, Xuetao Pei, Xie Xiaoyan, Fang Fang, Xu Lei, Lin Chen, Quan Zeng, Mingyi Qu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Platelets Blood Platelets Male Science Megakaryocyte differentiation General Physics and Astronomy Stem-cell differentiation Mice Transgenic General Biochemistry Genetics and Molecular Biology Article Cell Line Polyploidy 03 medical and health sciences 0302 clinical medicine Megakaryocyte Cell-Derived Microparticles medicine Animals Humans Platelet Platelet activation Progenitor cell lcsh:Science rhoB GTP-Binding Protein Thrombopoietin Megakaryopoiesis Multidisciplinary Base Sequence Chemistry Gene Expression Profiling Cell Differentiation General Chemistry Endocytosis Cell biology Mice Inbred C57BL Haematopoiesis MicroRNAs 030104 developmental biology medicine.anatomical_structure Liver 030220 oncology & carcinogenesis lcsh:Q Megakaryocytes |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2041-1723 |
| Popis: | 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. Platelets derive from megakaryocytes, which differentiate from hematopoietic stem/progenitor cells (HSPCs). Here, Qu et al show that platelet-derived microparticles carrying miR-1915-3p target HSPCs and promote megakaryopoiesis by suppressing RHOB expression levels. |
| Databáze: | OpenAIRE |
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