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SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart.
Valkov, Nedyalka; Das, Avash; Tucker, Nathan R; Li, Guoping; Salvador, Ane M; Chaffin, Mark D; Pereira De Oliveira Junior, Getulio; Kur, Ivan; Gokulnath, Priyanka; Ziegler, Olivia; Yeri, Ashish; Lu, Shulin; Khamesra, Aushee; Xiao, Chunyang; Rodosthenous, Rodosthenis; Srinivasan, Srimeenakshi; Toxavidis, Vasilis; Tigges, John; Laurent, Louise C; Momma, Stefan; Kitchen, Robert; Ellinor, Patrick; Ghiran, Ionita; Das, Saumya.
Afiliação
  • Valkov N; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Das A; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Tucker NR; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Li G; Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Salvador AM; Masonic Medical Research Institute, Utica, NY, USA.
  • Chaffin MD; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Pereira De Oliveira Junior G; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Kur I; Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Gokulnath P; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Ziegler O; Institute of Neurology (Edinger Institute), University Hospital, Goethe University, Frankfurt am Main, Germany.
  • Yeri A; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Lu S; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Khamesra A; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Xiao C; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Rodosthenous R; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Srinivasan S; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Toxavidis V; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Tigges J; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, CA, USA.
  • Laurent LC; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Momma S; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Kitchen R; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, CA, USA.
  • Ellinor P; Institute of Neurology (Edinger Institute), University Hospital, Goethe University, Frankfurt am Main, Germany.
  • Ghiran I; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Das S; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Life Sci Alliance ; 4(12)2021 12.
Article em En | MEDLINE | ID: mdl-34663679
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Nuclear / Transdução de Sinais / Eritrócitos / Análise de Célula Única / Vesículas Extracelulares / RNA-Seq / Insuficiência Cardíaca / Infarto do Miocárdio / Miocárdio Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Nuclear / Transdução de Sinais / Eritrócitos / Análise de Célula Única / Vesículas Extracelulares / RNA-Seq / Insuficiência Cardíaca / Infarto do Miocárdio / Miocárdio Idioma: En Ano de publicação: 2021 Tipo de documento: Article