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Thromb Haemost 2017; 117(05): 948-961
DOI: 10.1160/TH16-11-0873
Cellular Haemostasis and Platelets
Schattauer GmbH

The role of RNA uptake in platelet heterogeneity

Lauren Clancy
1   University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts, USA
,
Lea M. Beaulieu
1   University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts, USA
,
Kahraman Tanriverdi
1   University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts, USA
,
Jane E. Freedman
1   University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts, USA
› Author Affiliations Financial support: This work was supported by N01-HC 25195, P01-HL085381 (to J. E. Freedman); UH2TR000921 and U01HL126495 (to J. E. Freedman), are supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director.
Further Information

Publication History

Received: 21 November 2016

Accepted after major revision: 10 February 2017

Publication Date:
13 November 2017 (online)

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Summary

The role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated platelets is biologically functional and may transfer to other vascular cells, we hypothesised that platelet RNA diminishes over the lifespan of the platelet with diminishing platelet size due to horizontal cellular transfer. The purpose of this study is to determine if platelet RNA variance is the result of horizontal cellular transfer between platelets and other vascular cells. Utilising platelet sorting and RNA sequencing, we found that smaller platelets contained a more diverse set of transcripts than larger platelets. Further investigation using fluorescence imaging, gene expression analyses and in vitro and in vivo modelling revealed that platelets take up RNA from other vascular cells in a complex manner, revealing a dynamic role for platelets in modulating vascular homeostasis through bidirectional RNA transfer. The resultant RNA profile heterogeneity suggests unique functional roles for platelets dependent on size and complexity. This study expands our basic understanding of platelet function and heterogeneity and is the first to evaluate endogenous vascular RNA uptake and its relation to platelet processes. Our findings describe a novel endogenous phenomenon that can help elucidate the platelet’s role in these non-thrombotic and haemostatic fields, as well as present potential for diagnostic and therapeutic development.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Platelets - platelet physiology - RNA transfer - RNA uptake

 

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