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Alliance"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>Extracellular vesicles (EVs) mediate intercellular signaling by transferring their cargo to recipient cells, but the functional consequences of signaling are not fully appreciated. RBC-derived EVs are abundant in circulation and have been implicated in regulating immune responses. Here, we use a transgenic mouse model for fluorescence-based mapping of RBC-EV recipient cells to assess the role of this intercellular signaling mechanism in heart disease. Using fluorescent-based mapping, we detected an increase in RBC-EV\u2013targeted cardiomyocytes in a murine model of ischemic heart failure. Single cell nuclear RNA sequencing of the heart revealed a complex landscape of cardiac cells targeted by RBC-EVs, with enrichment of genes implicated in cell proliferation and stress signaling pathways compared with non-targeted cells. Correspondingly, cardiomyocytes targeted by RBC-EVs more frequently express cellular markers of DNA synthesis, suggesting the functional significance of EV-mediated signaling. In conclusion, our mouse model for mapping of EV-recipient cells reveals a complex cellular network of RBC-EV\u2013mediated intercellular communication in ischemic heart failure and suggests a functional role for this mode of intercellular signaling.<\/jats:p>","DOI":"10.26508\/lsa.202101048","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T15:57:02Z","timestamp":1634572622000},"page":"e202101048","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart"],"prefix":"10.26508","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3947-9947","authenticated-orcid":true,"given":"Nedyalka","family":"Valkov","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 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