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Endothelial cell cycle state determines propensity for arterial-venous fate

Author

Listed:
  • Nicholas W. Chavkin

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Gael Genet

    (University of Virginia School of Medicine)

  • Mathilde Poulet

    (Yale Cardiovascular Research Center Yale University School of Medicine)

  • Erin D. Jeffery

    (University of Virginia School of Medicine)

  • Corina Marziano

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Nafiisha Genet

    (University of Virginia School of Medicine)

  • Hema Vasavada

    (Yale Cardiovascular Research Center Yale University School of Medicine)

  • Elizabeth A. Nelson

    (University of Virginia School of Medicine)

  • Bipul R. Acharya

    (University of Virginia School of Medicine)

  • Anupreet Kour

    (University of Virginia School of Medicine)

  • Jordon Aragon

    (University of Virginia School of Medicine)

  • Stephanie P. McDonnell

    (University of Virginia School of Medicine)

  • Mahalia Huba

    (University of Virginia School of Medicine)

  • Gloria M. Sheynkman

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine
    UVA Comprehensive Cancer Center, University of Virginia)

  • Kenneth Walsh

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Karen K. Hirschi

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    Yale Cardiovascular Research Center Yale University School of Medicine)

Abstract

During blood vessel development, endothelial cells become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, and removes metabolic waste from, all tissues. Arterial-venous specification occurs in conjunction with suppression of endothelial cell cycle progression; however, the mechanistic role of cell cycle state is unknown. Herein, using Cdh5-CreERT2;R26FUCCI2aR reporter mice, we find that venous endothelial cells are enriched for the FUCCI-Negative state (early G1) and BMP signaling, while arterial endothelial cells are enriched for the FUCCI-Red state (late G1) and TGF-β signaling. Furthermore, early G1 state is essential for BMP4-induced venous gene expression, whereas late G1 state is essential for TGF-β1-induced arterial gene expression. Pharmacologically induced cell cycle arrest prevents arterial-venous specification defects in mice with endothelial hyperproliferation. Collectively, our results show that distinct endothelial cell cycle states provide distinct windows of opportunity for the molecular induction of arterial vs. venous fate.

Suggested Citation

  • Nicholas W. Chavkin & Gael Genet & Mathilde Poulet & Erin D. Jeffery & Corina Marziano & Nafiisha Genet & Hema Vasavada & Elizabeth A. Nelson & Bipul R. Acharya & Anupreet Kour & Jordon Aragon & Steph, 2022. "Endothelial cell cycle state determines propensity for arterial-venous fate," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33324-7
    DOI: 10.1038/s41467-022-33324-7
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    1. Gregory Farber & Yanhan Dong & Qiaozi Wang & Mitesh Rathod & Haofei Wang & Michelle Dixit & Benjamin Keepers & Yifang Xie & Kendall Butz & William J. Polacheck & Jiandong Liu & Li Qian, 2024. "Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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