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Angiocrine functions of organ-specific endothelial cells

Abstract

Endothelial cells that line capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establishes specialized vascular niches that deploy sets of growth factors, known as angiocrine factors. These cues participate actively in the induction, specification, patterning and guidance of organ regeneration, as well as in the maintainance of homeostasis and metabolism. When upregulated following injury, they orchestrate self-renewal and differentiation of tissue-specific resident stem and progenitor cells into functional organs. Uncovering the mechanisms by which organotypic endothelium distributes physiological levels of angiocrine factors both spatially and temporally will lay the foundation for clinical trials that promote organ repair without scarring.

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Figure 1: Specialized structures of capillary ECs and their crosstalk with parenchymal and stem cells.
Figure 2: Tissue-specific ECs orchestrate self-renewal and differentiation of stem and progenitors cells by supplying membrane-bound and secreted angiocrine factors.
Figure 3: Angiocrine signals support regeneration of hepatocytes and lung epithelial cells after injury.

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Acknowledgements

We acknowledge R. Nachman, D. Hajjar and the late A. Marcus and J. Folkman, whose pioneering work in vascular biology inspired us to uncover the instructive functions of endothelial cells. We thank our colleagues W. Schachterle, M. Poulos, K. Shido, S. Rabbany, P. Kermani, R. Lis, M. Seandel, A. Rafii, D. James, J. Scandura, M. Ginsberg, D. Nolan, G. Davis, Z. Rosenwaks, M. Sadelain, I. Riviere and J. Port for critical review and scientific input. We are grateful to Z. Cao for providing expertise in artwork. We apologize to those scientists whose work we could not highlight owing to space limitations. S.R. was supported by the Ansary Stem Cell Institute, the Empire State Stem Cell Board and New York State Department of Health (C026878, C028117 and C029156), the Howard Hughes Medical Institute, the US National Heart, Lung, and Blood Institute (R01HL115128, R01HL119872 and R01HL128158), the US National Cancer Institute (U54CA163167), the US National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095039) and the Qatar National Priorities Research Program (NPRP 6-131-3-268). J.M.B was supported by the Ansary Stem Cell Institute, an American Society of Hematology Scholar Award, an American Federation for Aging Research grant and a Leukemia and Lymphoma Society Quest for Cures award. B.-S.D was supported by the Ansary Stem Cell Institute and the American Heart Association (12SDG1213004).

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Correspondence to Shahin Rafii, Jason M. Butler or Bi-Sen Ding.

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S.R. is the founder of and an unpaid consultant to Angiocrine Bioscience, New York, New York 10028, USA. J.M.B receives research funding from Angiocrine Bioscience.

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Rafii, S., Butler, J. & Ding, BS. Angiocrine functions of organ-specific endothelial cells. Nature 529, 316–325 (2016). https://doi.org/10.1038/nature17040

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