SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart
Open Access
- 18 October 2021
- journal article
- research article
- Published by Life Science Alliance, LLC in Life Science Alliance
- Vol. 4 (12), e202101048
- https://doi.org/10.26508/lsa.202101048
Abstract
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.Funding Information
- NCATS, NHLBI (T32GM007276, UG3 TR002878, UG3 HL147353, RO1 HL150401, R35HL150807)
- SM DFG (MO2211-2)
- Edinger Foundation
This publication has 80 references indexed in Scilit:
- Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturationeLife, 2013
- Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through METNature Medicine, 2012
- ExoCarta 2012: database of exosomal proteins, RNA and lipidsNucleic Acids Research, 2011
- Sudden Cardiac Death Prediction and PreventionJournal of the American College of Cardiology, 2010
- Novel interactors and a role for supervillin in early cytokinesisCytoskeleton, 2010
- Membrane vesicles as conveyors of immune responsesNature Reviews Immunology, 2009
- Evidence for Cardiomyocyte Renewal in HumansScience, 2009
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cellsNature, 2007