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Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure.
Simonson, Bridget; Chaffin, Mark; Hill, Matthew C; Atwa, Ondine; Guedira, Yasmine; Bhasin, Harshit; Hall, Amelia W; Hayat, Sikander; Baumgart, Simon; Bedi, Kenneth C; Margulies, Kenneth B; Klattenhoff, Carla A; Ellinor, Patrick T.
Afiliación
  • Simonson B; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Chaffin M; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hill MC; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Atwa O; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Guedira Y; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Bhasin H; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hall AW; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Gene Regulation Observatory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hayat S; Precision Cardiology Laboratory, Bayer US, LLC, Cambridge, MA 02142, USA.
  • Baumgart S; Precision Cardiology Laboratory, Bayer US, LLC, Cambridge, MA 02142, USA.
  • Bedi KC; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Margulies KB; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Klattenhoff CA; Precision Cardiology Laboratory, Bayer US, LLC, Cambridge, MA 02142, USA.
  • Ellinor PT; Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic ad
Cell Rep ; 42(2): 112086, 2023 02 28.
Article en En | MEDLINE | ID: mdl-36790929
ABSTRACT
Ischemic cardiomyopathy (ICM) is the leading cause of heart failure worldwide, yet the cellular and molecular signature of this disease is largely unclear. Using single-nucleus RNA sequencing (snRNA-seq) and integrated computational analyses, we profile the transcriptomes of over 99,000 human cardiac nuclei from the non-infarct region of the left ventricle of 7 ICM transplant recipients and 8 non-failing (NF) controls. We find the cellular composition of the ischemic heart is significantly altered, with decreased cardiomyocytes and increased proportions of lymphatic, angiogenic, and arterial endothelial cells in patients with ICM. We show that there is increased LAMININ signaling from endothelial cells to other cell types in ICM compared with NF. Finally, we find that the transcriptional changes that occur in ICM are similar to those in hypertrophic and dilated cardiomyopathies and that the mining of these combined datasets can identify druggable genes that could be used to target end-stage heart failure.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cardiomiopatía Dilatada / Isquemia Miocárdica / Insuficiencia Cardíaca / Cardiomiopatías Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cardiomiopatía Dilatada / Isquemia Miocárdica / Insuficiencia Cardíaca / Cardiomiopatías Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos