TY - JOUR
T1 - Emerging Technologies for Understanding Platelet Diversity
AU - Heemskerk, Johan W M
AU - West, Jonathan
N1 - Funding Information:
This work is supported by the Landsteiner Foundation for Blood Transfusion Research Grant (No. 1711, J.W.M. Heemskerk), the British Heart Foundation (FS/13/67/30473, J. West) and the Medical Research Council (MC_PC_15078, J. West).
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/5
Y1 - 2022/5
N2 - This review discusses our understanding of platelet diversity with implications for the roles of platelets in hemostasis and thrombosis and identifies advanced technologies set to provide new insights. We use the term diversity to capture intrasubject platelet variability that can be intrinsic or governed by the environment and lead to a heterogeneous response pattern of aggregation, clot promotion, and external communication. Using choice examples, we discuss how the use of advanced technologies can provide new insights into the underlying causes of platelet molecular, structural, and functional diversity. As sources of diversity, we discuss the proliferating megakaryocytes with different allele-specific expression patterns, the asymmetrical formation of proplatelets, changes in platelets induced by aging and priming, interplatelet heterogeneity in thrombus organization and stability, and platelet-dependent communications. We provide indications how current knowledge gaps can be addressed using promising technologies, such as next-generation sequencing, proteomic approaches, advanced imaging techniques, multicolor flow and mass cytometry, multifunctional microfluidics assays, and organ-on-a-chip platforms. We then argue how this technology base can aid in characterizing platelet populations and in identifying platelet biomarkers relevant for the treatment of cardiovascular disease.
AB - This review discusses our understanding of platelet diversity with implications for the roles of platelets in hemostasis and thrombosis and identifies advanced technologies set to provide new insights. We use the term diversity to capture intrasubject platelet variability that can be intrinsic or governed by the environment and lead to a heterogeneous response pattern of aggregation, clot promotion, and external communication. Using choice examples, we discuss how the use of advanced technologies can provide new insights into the underlying causes of platelet molecular, structural, and functional diversity. As sources of diversity, we discuss the proliferating megakaryocytes with different allele-specific expression patterns, the asymmetrical formation of proplatelets, changes in platelets induced by aging and priming, interplatelet heterogeneity in thrombus organization and stability, and platelet-dependent communications. We provide indications how current knowledge gaps can be addressed using promising technologies, such as next-generation sequencing, proteomic approaches, advanced imaging techniques, multicolor flow and mass cytometry, multifunctional microfluidics assays, and organ-on-a-chip platforms. We then argue how this technology base can aid in characterizing platelet populations and in identifying platelet biomarkers relevant for the treatment of cardiovascular disease.
KW - COLLAGEN
KW - EXPRESSION
KW - MEGAKARYOCYTE
KW - MESSENGER-RNA
KW - RETICULATED PLATELETS
KW - SECRETION
KW - SINGLE
KW - SUPERRESOLUTION MICROSCOPY
KW - TRANSCRIPTOME
KW - VISUALIZATION
KW - biomarkers
KW - cardiovascular diseases
KW - hemostasis
KW - megakaryocytes
KW - platelets
KW - thrombosis
U2 - 10.1161/atvbaha.121.317092
DO - 10.1161/atvbaha.121.317092
M3 - (Systematic) Review article
C2 - 35296153
SN - 1079-5642
VL - 42
SP - 540
EP - 552
JO - Arteriosclerosis Thrombosis and Vascular Biology
JF - Arteriosclerosis Thrombosis and Vascular Biology
IS - 5
ER -