TY - JOUR T1 - SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101048 VL - 4 IS - 12 SP - e202101048 AU - Nedyalka Valkov AU - Avash Das AU - Nathan R Tucker AU - Guoping Li AU - Ane M Salvador AU - Mark D Chaffin AU - Getulio Pereira De Oliveira Junior AU - Ivan Kur AU - Priyanka Gokulnath AU - Olivia Ziegler AU - Ashish Yeri AU - Shulin Lu AU - Aushee Khamesra AU - Chunyang Xiao AU - Rodosthenis Rodosthenous AU - Srimeenakshi Srinivasan AU - Vasilis Toxavidis AU - John Tigges AU - Louise C Laurent AU - Stefan Momma AU - Robert Kitchen AU - Patrick Ellinor AU - Ionita Ghiran AU - Saumya Das Y1 - 2021/12/01 UR - https://www.life-science-alliance.org/content/4/12/e202101048.abstract N2 - 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–targeted 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–mediated intercellular communication in ischemic heart failure and suggests a functional role for this mode of intercellular signaling. ER -