Single platelet variability governs population sensitivity and initiates intrinsic heterotypic responses
Single platelet variability governs population sensitivity and initiates intrinsic heterotypic responses
Investigations into the nature of platelet functional variety and consequences for homeostasis require new methods for resolving single platelet phenotypes. Here we combine droplet microfluidics with flow cytometry for high throughput single platelet function analysis. A large-scale sensitivity continuum was shown to be a general feature of human platelets from individual donors, with hypersensitive platelets coordinating significant sensitivity gains in bulk platelet populations and shown to direct aggregation in droplet-confined minimal platelet systems. Sensitivity gains scaled with agonist potency (convulxin > TRAP-14>ADP) and reduced the collagen and thrombin activation threshold required for platelet population polarization into pro-aggregatory and pro-coagulant states. The heterotypic platelet response results from an intrinsic behavioural program. The method and findings invite future discoveries into the nature of hypersensitive platelets and how community effects produce population level responses in health and disease.
Jongen, Maaike S.A.
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Macarthur, Ben D.
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Englyst, Nicola A.
f84399af-7265-4224-b556-102c3aa272b0
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
4 June 2020
Jongen, Maaike S.A.
13f00bd0-5bf2-400f-a3ac-aa90d2180327
Macarthur, Ben D.
2c0476e7-5d3e-4064-81bb-104e8e88bb6b
Englyst, Nicola A.
f84399af-7265-4224-b556-102c3aa272b0
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Jongen, Maaike S.A., Macarthur, Ben D., Englyst, Nicola A. and West, Jonathan
(2020)
Single platelet variability governs population sensitivity and initiates intrinsic heterotypic responses.
Communications Biology, 3, [281].
(doi:10.1101/2020.01.22.915512).
Abstract
Investigations into the nature of platelet functional variety and consequences for homeostasis require new methods for resolving single platelet phenotypes. Here we combine droplet microfluidics with flow cytometry for high throughput single platelet function analysis. A large-scale sensitivity continuum was shown to be a general feature of human platelets from individual donors, with hypersensitive platelets coordinating significant sensitivity gains in bulk platelet populations and shown to direct aggregation in droplet-confined minimal platelet systems. Sensitivity gains scaled with agonist potency (convulxin > TRAP-14>ADP) and reduced the collagen and thrombin activation threshold required for platelet population polarization into pro-aggregatory and pro-coagulant states. The heterotypic platelet response results from an intrinsic behavioural program. The method and findings invite future discoveries into the nature of hypersensitive platelets and how community effects produce population level responses in health and disease.
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s42003-020-1002-5 (1)
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Submitted date: 23 January 2020
Accepted/In Press date: 12 May 2020
e-pub ahead of print date: 4 June 2020
Published date: 4 June 2020
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Local EPrints ID: 438193
URI: http://eprints.soton.ac.uk/id/eprint/438193
ISSN: 2399-3642
PURE UUID: 4c4bc8ef-24b5-47ca-b2a9-8da1654cbe79
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Date deposited: 04 Mar 2020 17:30
Last modified: 17 Mar 2024 03:29
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Author:
Maaike S.A. Jongen
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