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Circ Res. 2016 Feb 5;118(3):400-9. doi: 10.1161/CIRCRESAHA.115.307778. Epub 2015 Dec 3.

Revisiting Cardiac Cellular Composition.

Author information

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.

KEYWORDS:

endothelial cells; fibroblasts; flow cytometry; heart; leukocytes

Comment in

PMID:
26635390
PMCID:
PMC4744092
DOI:
10.1161/CIRCRESAHA.115.307778
[Indexed for MEDLINE]
Free PMC Article

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