One Health horsepower in hemostasis: SEL1Lecting stable platelet adhesion
Caitlin D. Schneider, James P. Luyendyk
Caitlin D. Schneider, James P. Luyendyk
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Commentary

One Health horsepower in hemostasis: SEL1Lecting stable platelet adhesion

Abstract

Comparative biology approaches have produced foundational discoveries in the mechanisms underlying thrombosis and hemostasis. In this issue of the JCI, work by Dahlgren and colleagues continues in this tradition using an approach that integrated a multispecies investigation of conserved function with genomic exploration and discovery. Dahlgren et al. describe the identification of pathogenic variants in the ER-associated degradation pathway protein SEL1L in a rare platelet disorder affecting horses. After establishing a conserved role for SEL1L in zebrafish, mouse, and human platelet function, the study found evidence for SEL1L variants in association with bleeding phenotypes in human GWAS. Altogether, the findings elucidate a previously unrecognized component of platelet function, laying the groundwork for mechanistic explanation of a subset of human bleeding phenotypes and providing a powerful endorsement of integrative, collaborative research.

Authors

Caitlin D. Schneider, James P. Luyendyk

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Figure 1

Multispecies research to advance understanding of bleeding disorders.

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Multispecies research to advance understanding of bleeding disorders. Da...
Dahlgren et al. (3) used a multispecies One Heath–framed approach to uncover mechanisms underlying AET, a rare bleeding disorder in horses. After identifying missense mutations in SEL1L in the equine disease, mechanistic implications were determined using mice, zebrafish, and human platelets, and the translational implications include identification of variants of SEL1L potentially connected to bleeding disorders of unknown origin in humans. There is abundant potential for this approach, pairing challenges in veterinary and human medicine, to address smoldering challenges in the field of hemostasis and thrombosis.