SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart

Life Sci Alliance. 2021 Oct 18;4(12):e202101048. doi: 10.26508/lsa.202101048. Print 2021 Dec.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Disease Models, Animal
  • Erythrocytes / metabolism*
  • Extracellular Vesicles / metabolism*
  • Female
  • Healthy Volunteers
  • Heart Failure / blood*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardial Infarction / blood*
  • Myocardium / metabolism*
  • Myocytes, Cardiac / metabolism
  • RNA, Nuclear / genetics*
  • RNA-Seq / methods*
  • Signal Transduction / genetics*
  • Single-Cell Analysis / methods*


  • RNA, Nuclear

Associated data

  • Dryad/10.5061/dryad.vhhmgqnv9