Human Organ-Specific Endothelial Cell Heterogeneity
Raluca Marcu,
Yoon Jung Choi,
Jun Xue,
Chelsea L. Fortin,
Yuliang Wang,
Ryan J. Nagao,
Jin Xu,
James W. MacDonald,
Theo K. Bammler,
Charles E. Murry,
Kimberly Muczynski,
Kelly R. Stevens,
Jonathan Himmelfarb,
Stephen M. Schwartz,
Ying Zheng
Affiliations
Raluca Marcu
Department of Bioengineering, University of Washington, Seattle, WA, USA
Yoon Jung Choi
Department of Bioengineering, University of Washington, Seattle, WA, USA
Jun Xue
Department of Bioengineering, University of Washington, Seattle, WA, USA
Chelsea L. Fortin
Department of Pathology, University of Washington, Seattle, WA, USA
Yuliang Wang
Department of Computer Science & Engineering, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
Ryan J. Nagao
Department of Bioengineering, University of Washington, Seattle, WA, USA
Jin Xu
Department of Bioengineering, University of Washington, Seattle, WA, USA
James W. MacDonald
Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
Theo K. Bammler
Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
Charles E. Murry
Department of Bioengineering, University of Washington, Seattle, WA, USA; Department of Pathology, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA
Kimberly Muczynski
Department of Medicine, University of Washington, Seattle, WA, USA
Kelly R. Stevens
Department of Bioengineering, University of Washington, Seattle, WA, USA; Department of Pathology, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
Jonathan Himmelfarb
Department of Medicine, University of Washington, Seattle, WA, USA; Kidney Research Institute, University of Washington, Seattle, WA, USA
Stephen M. Schwartz
Department of Pathology, University of Washington, Seattle, WA, USA
Ying Zheng
Department of Bioengineering, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA; Kidney Research Institute, University of Washington, Seattle, WA, USA; Corresponding author
Summary: The endothelium first forms in the blood islands in the extra-embryonic yolk sac and then throughout the embryo to establish circulatory networks that further acquire organ-specific properties during development to support diverse organ functions. Here, we investigated the properties of endothelial cells (ECs), isolated from four human major organs—the heart, lung, liver, and kidneys—in individual fetal tissues at three months' gestation, at gene expression, and at cellular function levels. We showed that organ-specific ECs have distinct expression patterns of gene clusters, which support their specific organ development and functions. These ECs displayed distinct barrier properties, angiogenic potential, and metabolic rate and support specific organ functions. Our findings showed the link between human EC heterogeneity and organ development and can be exploited therapeutically to contribute in organ regeneration, disease modeling, as well as guiding differentiation of tissue-specific ECs from human pluripotent stem cells. : Stem Cells Research; Developmental Biology; Biology of Human Development Subject Areas: Stem Cells Research, Developmental Biology, Biology of Human Development
