title: Revisiting Cardiac Cellular Composition.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pinto
authors.affiliation: 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.).
authors.forename: Alexei
authors.initials: A
authors.lastname: Ilinykh
authors.affiliation: 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.).
authors.forename: Malina J
authors.initials: MJ
authors.lastname: Ivey
authors.affiliation: 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.).
authors.forename: Jill T
authors.initials: JT
authors.lastname: Kuwabara
authors.affiliation: 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.).
authors.forename: Michelle L
authors.initials: ML
authors.lastname: D'Antoni
authors.affiliation: 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.).
authors.forename: Ryan
authors.initials: R
authors.lastname: Debuque
authors.affiliation: 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.).
authors.forename: Anjana
authors.initials: A
authors.lastname: Chandran
authors.affiliation: 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.).
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.).
authors.forename: Komal
authors.initials: K
authors.lastname: Arora
authors.affiliation: 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.).
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Rosenthal
authors.affiliation: 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.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tallquist
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006321:Heart; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D010641:Phenotype
chemical_list: D015415:Biomarkers; D049452:Green Fluorescent Proteins
keywords: endothelial cells; fibroblasts; flow cytometry; heart; leukocytes