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Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p
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 ve...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532443/ https://www.ncbi.nlm.nih.gov/pubmed/33009394 http://dx.doi.org/10.1038/s41467-020-18802-0 |
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author | Qu, Mingyi Zou, Xiaojing Fang, Fang Wang, Shouye Xu, Lei Zeng, Quan Fan, Zeng Chen, Lin Yue, Wen Xie, Xiaoyan Pei, Xuetao |
author_facet | Qu, Mingyi Zou, Xiaojing Fang, Fang Wang, Shouye Xu, Lei Zeng, Quan Fan, Zeng Chen, Lin Yue, Wen Xie, Xiaoyan Pei, Xuetao |
author_sort | Qu, Mingyi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7532443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75324432020-10-19 Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p Qu, Mingyi Zou, Xiaojing Fang, Fang Wang, Shouye Xu, Lei Zeng, Quan Fan, Zeng Chen, Lin Yue, Wen Xie, Xiaoyan Pei, Xuetao Nat Commun Article 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. Nature Publishing Group UK 2020-10-02 /pmc/articles/PMC7532443/ /pubmed/33009394 http://dx.doi.org/10.1038/s41467-020-18802-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Qu, Mingyi Zou, Xiaojing Fang, Fang Wang, Shouye Xu, Lei Zeng, Quan Fan, Zeng Chen, Lin Yue, Wen Xie, Xiaoyan Pei, Xuetao Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p |
title | Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p |
title_full | Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p |
title_fullStr | Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p |
title_full_unstemmed | Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p |
title_short | Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p |
title_sort | platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via mir-1915-3p |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532443/ https://www.ncbi.nlm.nih.gov/pubmed/33009394 http://dx.doi.org/10.1038/s41467-020-18802-0 |
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