Revisiting Cardiac Cellular Composition

• Published in: Circulation research Vol. 118; no. 3; pp. 400 - 409
• Main Authors: Pinto, Alexander R, Ilinykh, Alexei, Ivey, Malina J, Kuwabara, Jill T, D’Antoni, Michelle L, Debuque, Ryan, Chandran, Anjana, Wang, Lina, Arora, Komal, Rosenthal, Nadia A, Tallquist, Michelle D
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 05-02-2016
• Subjects: Adult; Animals; Biomarkers - metabolism; Cell Count; Cell Differentiation; Cell Lineage; Cell Separation - methods; Endothelial Cells - metabolism; Female; Fibroblasts - metabolism; Flow Cytometry; Gene Expression Regulation; Green Fluorescent Proteins - biosynthesis; Green Fluorescent Proteins - genetics; Heart; Hematopoietic Stem Cells - metabolism; Humans; Immunohistochemistry; Male; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Phenotype; leukocytes; endothelial cells; fibroblasts; flow cytometry; heart
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.115.307778

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.