SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart.
SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart.
复制标题
SnRNA测序定义了鼠心中rbc衍生的细胞外囊泡的信号传导。
DOI：
10.26508/lsa.202101048
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发表时间：
2021-12
影响因子：
4.4
通讯作者：
Das S
中科院分区：
文献类型：
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作者：
Valkov N;Das A;Tucker NR;Li G;Salvador AM;Chaffin MD;Pereira De Oliveira Junior G;Kur I;Gokulnath P;Ziegler O;Yeri A;Lu S;Khamesra A;Xiao C;Rodosthenous R;Srinivasan S;Toxavidis V;Tigges J;Laurent LC;Momma S;Kitchen R;Ellinor P;Ghiran I;Das S
In a unique model of fluorescent based mapping of EV recipient cells, RBC-EVs were found to signal to cardiac cells and regulate gene expression in a model of ischemic heart failure. 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.
