IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33324-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33324-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-33324-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Tianying Su & Geoff Stanley & Rahul Sinha & Gaetano D’Amato & Soumya Das & Siyeon Rhee & Andrew H. Chang & Aruna Poduri & Brian Raftrey & Thanh Theresa Dinh & Walter A. Roper & Guang Li & Kelsey E. Qu, 2018. "Single-cell analysis of early progenitor cells that build coronary arteries," Nature, Nature, vol. 559(7714), pages 356-362, July.
    2. Cong Xu & Sana S. Hasan & Inga Schmidt & Susana F. Rocha & Mara E. Pitulescu & Jeroen Bussmann & Dana Meyen & Erez Raz & Ralf H. Adams & Arndt F. Siekmann, 2014. "Arteries are formed by vein-derived endothelial tip cells," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    3. Wen Luo & Irene Garcia-Gonzalez & Macarena Fernández-Chacón & Verónica Casquero-Garcia & Maria S. Sanchez-Muñoz & Severin Mühleder & Lourdes Garcia-Ortega & Jorge Andrade & Michael Potente & Rui Bened, 2021. "Arterialization requires the timely suppression of cell growth," Nature, Nature, vol. 589(7842), pages 437-441, January.
    4. Monica Corada & Fabrizio Orsenigo & Marco Francesco Morini & Mara Elena Pitulescu & Ganesh Bhat & Daniel Nyqvist & Ferruccio Breviario & Valentina Conti & Anais Briot & M. Luisa Iruela-Arispe & Ralf H, 2013. "Sox17 is indispensable for acquisition and maintenance of arterial identity," Nature Communications, Nature, vol. 4(1), pages 1-14, December.
    5. Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabeth Ra, 2018. "Author Correction: A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 560(7716), pages 3-3, August.
    6. Wing Fuk Chan & Hannah D. Coughlan & Jie H. S. Zhou & Christine R. Keenan & Naiara G. Bediaga & Philip D. Hodgkin & Gordon K. Smyth & Timothy M. Johanson & Rhys S. Allan, 2021. "Pre-mitotic genome re-organisation bookends the B cell differentiation process," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    7. Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Del Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabet, 2018. "A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 554(7693), pages 475-480, February.
    8. Roxana Ola & Alexandre Dubrac & Jinah Han & Feng Zhang & Jennifer S. Fang & Bruno Larrivée & Monica Lee & Ana A. Urarte & Jan R. Kraehling & Gael Genet & Karen K. Hirschi & William C. Sessa & Francesc, 2016. "PI3 kinase inhibition improves vascular malformations in mouse models of hereditary haemorrhagic telangiectasia," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    9. Alice Neal & Svanhild Nornes & Sophie Payne & Marsha D. Wallace & Martin Fritzsche & Pakavarin Louphrasitthiphol & Robert N. Wilkinson & Kira M. Chouliaras & Ke Liu & Karen Plant & Radhika Sholapurkar, 2019. "Venous identity requires BMP signalling through ALK3," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    10. Alexander M. Simon & Daniel A. Goodenough & En Li & David L. Paul, 1997. "Female infertility in mice lacking connexin 37," Nature, Nature, vol. 385(6616), pages 525-529, February.
    11. Kevin P. Mouillesseaux & David S. Wiley & Lauren M. Saunders & Lyndsay A. Wylie & Erich J. Kushner & Diana C. Chong & Kathryn M. Citrin & Andrew T. Barber & Youngsook Park & Jun-Dae Kim & Leigh Ann Sa, 2016. "Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Laetitia Préau & Anna Lischke & Melanie Merkel & Neslihan Oegel & Maria Weissenbruch & Andria Michael & Hongryeol Park & Dietmar Gradl & Christian Kupatt & Ferdinand Noble, 2024. "Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    3. Airi Jo-Watanabe & Toshiki Inaba & Takahiro Osada & Ryota Hashimoto & Tomohiro Nishizawa & Toshiaki Okuno & Sayoko Ihara & Kazushige Touhara & Nobutaka Hattori & Masatsugu Oh-Hora & Osamu Nureki & Tak, 2024. "Bicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Xinrui Zhou & Wan Yi Seow & Norbert Ha & Teh How Cheng & Lingfan Jiang & Jeeranan Boonruangkan & Jolene Jie Lin Goh & Shyam Prabhakar & Nigel Chou & Kok Hao Chen, 2024. "Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Kevin Boyé & Luiz Henrique Geraldo & Jessica Furtado & Laurence Pibouin-Fragner & Mathilde Poulet & Doyeun Kim & Bryce Nelson & Yunling Xu & Laurent Jacob & Nawal Maissa & Dritan Agalliu & Lena Claess, 2022. "Endothelial Unc5B controls blood-brain barrier integrity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Amy J. Gleichman & Riki Kawaguchi & Michael V. Sofroniew & S. Thomas Carmichael, 2023. "A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Xiang He & Daiqin Xiong & Lei Zhao & Jialong Fu & Lingfei Luo, 2024. "Meningeal lymphatic supporting cells govern the formation and maintenance of zebrafish mural lymphatic endothelial cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Martin Uhrbom & Lars Muhl & Guillem Genové & Jianping Liu & Henrik Palmgren & Ida Alexandersson & Fredrik Karlsson & Alex-Xianghua Zhou & Sandra Lunnerdal & Sonja Gustafsson & Byambajav Buyandelger & , 2024. "Adipose stem cells are sexually dimorphic cells with dual roles as preadipocytes and resident fibroblasts," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. Shujuan Zhao & Kedous Y. Mekbib & Martijn A. Ent & Garrett Allington & Andrew Prendergast & Jocelyn E. Chau & Hannah Smith & John Shohfi & Jack Ocken & Daniel Duran & Charuta G. Furey & Le Thi Hao & P, 2023. "Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    10. Chris Greene & Nicole Hanley & Cristina R. Reschke & Avril Reddy & Maarja A. Mäe & Ruairi Connolly & Claire Behan & Eoin O’Keeffe & Isobel Bolger & Natalie Hudson & Conor Delaney & Michael A. Farrell , 2022. "Microvascular stabilization via blood-brain barrier regulation prevents seizure activity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. 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.
    12. Xiaomeng Wan & Jiashun Xiao & Sindy Sing Ting Tam & Mingxuan Cai & Ryohichi Sugimura & Yang Wang & Xiang Wan & Zhixiang Lin & Angela Ruohao Wu & Can Yang, 2023. "Integrating spatial and single-cell transcriptomics data using deep generative models with SpatialScope," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    13. Amira Sayed Hanafy & Pia Steinlein & Julika Pitsch & Mariella Hurtado Silva & Natascha Vana & Albert J. Becker & Mark Evan Graham & Susanne Schoch & Alf Lamprecht & Dirk Dietrich, 2023. "Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    14. Xin Rui Lim & Mohammad M. Abd-Alhaseeb & Michael Ippolito & Masayo Koide & Amanda J. Senatore & Curtis Plante & Ashwini Hariharan & Nick Weir & Thomas A. Longden & Kathryn A. Laprade & James M. Staffo, 2024. "Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    15. Martin Arostegui & R. Wilder Scott & Kerstin Böse & T. Michael Underhill, 2022. "Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    16. Moises Freitas-Andrade & Cesar H. Comin & Peter Dyken & Julie Ouellette & Joanna Raman-Nair & Nicole Blakeley & Qing Yan Liu & Sonia Leclerc & Youlian Pan & Ziying Liu & Micaël Carrier & Karan Thakur , 2023. "Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    17. Yutong Guo & Hohyun Lee & Chulyong Kim & Christian Park & Akane Yamamichi & Pavlina Chuntova & Marco Gallus & Miguel O. Bernabeu & Hideho Okada & Hanjoong Jo & Costas Arvanitis, 2024. "Ultrasound frequency-controlled microbubble dynamics in brain vessels regulate the enrichment of inflammatory pathways in the blood-brain barrier," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    18. Lin Wei Tung & Elena Groppa & Hesham Soliman & Bruce Lin & Chihkai Chang & Chun Wai Cheung & Morten Ritso & David Guo & Lucas Rempel & Sarthak Sinha & Christine Eisner & Julyanne Brassard & Kelly McNa, 2023. "Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    19. Xiaoyu Xue & Xianming Wu & Yongheng Fan & Shuyu Han & Haipeng Zhang & Yuting Sun & Yanyun Yin & Man Yin & Bing Chen & Zheng Sun & Shuaijing Zhao & Qi Zhang & Weiyuan Liu & Jiaojiao Zhang & Jiayin Li &, 2024. "Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. Jeremiah Bernier-Latmani & Cristina Mauri & Rachel Marcone & François Renevey & Stephan Durot & Liqun He & Michael Vanlandewijck & Catherine Maclachlan & Suzel Davanture & Nicola Zamboni & Graham W. K, 2022. "ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33324-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.