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dc.contributor.advisorJane E. Freedman, MD
dc.contributor.authorClancy, Lauren R.
dc.date2022-08-11T08:08:46.000
dc.date.accessioned2022-08-23T16:07:43Z
dc.date.available2022-08-23T16:07:43Z
dc.date.issued2017-08-22
dc.date.submitted2017-10-02
dc.identifier.doi10.13028/M2468G
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32304
dc.description.abstractAs our understanding of the platelet’s systemic role continues to expand beyond hemostasis and thrombosis, interrogation of the platelet’s ability to affect diverse biological processes is required. Studies of the platelet’s non-traditional roles have focused on developing our understanding of the platelet’s relation to specific disease phenotypes as well as elucidation of platelet characteristics, content, and function. The generic content, traditional function and heterogeneity of platelets have long been accepted; more ambiguous and controversial has been how these factors are interrelated. Investigation of platelet content revealed the presence of biologically functional RNA in anucleated platelets, the correlation of platelet RNA to distinct phenotypes, and the ability of platelets to transfer RNA to other vascular cells; however how these processes occur is unclear. To further interrogate platelet RNA processes, we utilized sorting and RNA sequencing to develop platelet subpopulation transcriptome profiles. We found that platelet heterogeneity extends to the platelet transcriptome: distinct RNA profiles exist dependent on platelet size. We hypothesized that this RNA heterogeneity is the result of RNA transfer between platelets and vascular cells. Using in vitro and in vivo modeling, we were able to show the novel ability of platelets to take up RNA from vascular cells, correlating to the unique functional profile associated with small platelet transcriptomes. These findings reveal a role for platelet RNA transfer in platelet RNA heterogeneity, with potential correlation to platelet functional diversity previously proposed. The ability of the platelet to bidirectionally transfer RNA within circulation has implications for vascular health and beyond.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectPlatelets
dc.subjectRNA
dc.subjectRNA uptake
dc.subjectBiology
dc.subjectCell Biology
dc.subjectTranslational Medical Research
dc.titlePlatelet Transcriptome Heterogeneity: A Role for RNA Uptake in Vascular Health and Disease
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1927&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/922
dc.legacy.embargo2019-10-02T00:00:00-07:00
dc.identifier.contextkey10844632
refterms.dateFOA2022-08-25T04:46:49Z
html.description.abstract<p>As our understanding of the platelet’s systemic role continues to expand beyond hemostasis and thrombosis, interrogation of the platelet’s ability to affect diverse biological processes is required. Studies of the platelet’s non-traditional roles have focused on developing our understanding of the platelet’s relation to specific disease phenotypes as well as elucidation of platelet characteristics, content, and function. The generic content, traditional function and heterogeneity of platelets have long been accepted; more ambiguous and controversial has been how these factors are interrelated.</p> <p>Investigation of platelet content revealed the presence of biologically functional RNA in anucleated platelets, the correlation of platelet RNA to distinct phenotypes, and the ability of platelets to transfer RNA to other vascular cells; however how these processes occur is unclear. To further interrogate platelet RNA processes, we utilized sorting and RNA sequencing to develop platelet subpopulation transcriptome profiles. We found that platelet heterogeneity extends to the platelet transcriptome: distinct RNA profiles exist dependent on platelet size. We hypothesized that this RNA heterogeneity is the result of RNA transfer between platelets and vascular cells. Using <em>in vitro</em> and <em>in vivo </em>modeling, we were able to show the novel ability of platelets to take up RNA from vascular cells, correlating to the unique functional profile associated with small platelet transcriptomes. These findings reveal a role for platelet RNA transfer in platelet RNA heterogeneity, with potential correlation to platelet functional diversity previously proposed. The ability of the platelet to bidirectionally transfer RNA within circulation has implications for vascular health and beyond.</p>
dc.identifier.submissionpathgsbs_diss/922
dc.contributor.departmentDepartment of Medicine, Cardiovascular Division
dc.description.thesisprogramTranslational Science
dc.identifier.orcid0000-0002-6596-421X


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