Alexander R Pinto1, Alexei Ilinykh2, Malina J Ivey2, Jill T Kuwabara2, Michelle L D'Antoni2, Ryan Debuque2, Anjana Chandran2, Lina Wang2, Komal Arora2, Nadia A Rosenthal2, Michelle D Tallquist1. 1. From the Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia (A.R.P., A.I., R.D., A.C., L.W., N.R.); Department of Medicine, Center for Cardiovascular Research (M.J.I., J.T.K., M.L.D'A., K.A., M.D.T.) and Department of Cellular and Molecular Biology (M.J.I., J.T.K.), University of Hawaii, Honolulu, HI; National Heart and Lung Institute, Imperial College London, London, United Kingdom (N.A.R.); and The Jackson Laboratory, Bar Harbor, ME (N.A.R.). michelle.tallquist@hawaii.edu alex.pinto@monash.edu. 2. From the Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia (A.R.P., A.I., R.D., A.C., L.W., N.R.); Department of Medicine, Center for Cardiovascular Research (M.J.I., J.T.K., M.L.D'A., K.A., M.D.T.) and Department of Cellular and Molecular Biology (M.J.I., J.T.K.), University of Hawaii, Honolulu, HI; National Heart and Lung Institute, Imperial College London, London, United Kingdom (N.A.R.); and The Jackson Laboratory, Bar Harbor, ME (N.A.R.).
Abstract
RATIONALE: Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration. OBJECTIVE: To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart. METHODS AND RESULTS: Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts <20% of the nonmyocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of nonmyocytes. High-dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and 2 commonly assigned fibroblast markers, Sca-1 and CD90, under-represent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population. CONCLUSIONS: This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of noncardiomyocytes and are likely to play a greater role in physiological function and response to injury than previously appreciated.
RATIONALE: Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration. OBJECTIVE: To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart. METHODS AND RESULTS: Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts <20% of the nonmyocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of nonmyocytes. High-dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and 2 commonly assigned fibroblast markers, Sca-1 and CD90, under-represent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population. CONCLUSIONS: This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of noncardiomyocytes and are likely to play a greater role in physiological function and response to injury than previously appreciated.
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Authors: Aida Oliván-Viguera; María Pérez-Zabalza; Laura García-Mendívil; Konstantinos A Mountris; Sofía Orós-Rodrigo; Estel Ramos-Marquès; José María Vallejo-Gil; Pedro Carlos Fresneda-Roldán; Javier Fañanás-Mastral; Manuel Vázquez-Sancho; Marta Matamala-Adell; Fernando Sorribas-Berjón; Javier André Bellido-Morales; Francisco Javier Mancebón-Sierra; Alexánder Sebastián Vaca-Núñez; Carlos Ballester-Cuenca; Miguel Ángel Marigil; Cristina Pastor; Laura Ordovás; Ralf Köhler; Emiliano Diez; Esther Pueyo Journal: Sci Rep Date: 2020-11-17 Impact factor: 4.379