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Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood-derived CD34+ Cells
Published on: December 27, 2017
Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p
Mingyi Qu1,2,3, Xiaojing Zou1, Fang Fang1,2,3
1Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine Beijing, Beijing, 100850, China.
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.
Insights
Platelet-derived microparticles (PMPs) promote platelet production by guiding hematopoietic stem/progenitor cells (HSPCs) to become megakakaryocytes. This process involves miR-1915-3p, enhancing platelet replenishment without altering thrombopoietin levels.
Area of Science:
- Hematology
- Molecular Biology
- Cell Biology
Background:
- Thrombosis causes platelet depletion, necessitating efficient replenishment from hematopoietic stem/progenitor cells (HSPCs).
- Platelet-derived microparticles (PMPs) are vesicles released from activated platelets, carrying proteins and RNA.
- The potential role of PMPs in regulating platelet production remains largely unexplored.
Purpose of the Study:
- To investigate whether PMPs influence platelet production from HSPCs.
- To elucidate the mechanism by which PMPs might regulate megakakaryopoiesis.
Main Methods:
- Induction of acute liver injury in mice to observe changes in megakaryocyte density and circulating PMPs.
- In vitro studies involving the incubation of HSPCs with PMPs.
- Analysis of miRNA transport and target gene suppression (Rho GTPase family member B) in HSPCs.
- Administration of PMPs to irradiated mice to assess effects on megakaryocyte and platelet counts.
Main Results:
- Acute liver injury in mice led to increased circulating PMPs and bone marrow megakaryocyte density, independent of thrombopoietin (TPO) levels.
- In vitro, PMPs were internalized by HSPCs, promoting their differentiation into megakaryocytes.
- miR-1915-3p, enriched in PMPs, was transferred to HSPCs, suppressing Rho GTPase family member B and inducing megakaryopoiesis.
- Direct PMP injection into mice increased megakaryocyte and platelet numbers without affecting TPO.
Conclusions:
- Platelet-derived microparticles (PMPs) play a significant role in promoting megakaryocytic differentiation and platelet production.
- The PMP-mediated pathway, involving miR-1915-3p, offers a novel mechanism for regulating platelet homeostasis.
- These findings suggest PMPs as potential therapeutic agents for conditions involving platelet deficiency.
