IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41279-6.html
   My bibliography  Save this article

Cell diversity and plasticity during atrioventricular heart valve EMTs

Author

Listed:
  • Jeremy Lotto

    (BC Cancer
    University of British Columbia)

  • Rebecca Cullum

    (BC Cancer)

  • Sibyl Drissler

    (BC Cancer
    University of British Columbia)

  • Martin Arostegui

    (University of British Columbia
    University of British Columbia)

  • Victoria C. Garside

    (BC Cancer
    University of British Columbia
    University of Melbourne)

  • Bettina M. Fuglerud

    (BC Cancer
    University of British Columbia)

  • Makenna Clement-Ranney

    (BC Cancer)

  • Avinash Thakur

    (BC Cancer
    University of British Columbia)

  • T. Michael Underhill

    (University of British Columbia
    University of British Columbia
    University of British Columbia)

  • Pamela A. Hoodless

    (BC Cancer
    University of British Columbia
    University of British Columbia
    University of British Columbia)

Abstract

Epithelial-to-mesenchymal transitions (EMTs) of both endocardium and epicardium guide atrioventricular heart valve formation, but the cellular complexity and small scale of this tissue have restricted analyses. To circumvent these issues, we analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 hearts to E12.5 atrioventricular canals. We delineate mesenchymal and endocardial bifurcation during endocardial EMT, identify a distinct, transdifferentiating epicardial population during epicardial EMT, and reveal the activation of epithelial-mesenchymal plasticity during both processes. In Sox9-deficient valves, we observe increased epithelial-mesenchymal plasticity, indicating a role for SOX9 in promoting endothelial and mesenchymal cell fate decisions. Lastly, we deconvolve cell interactions guiding the initiation and progression of cardiac valve EMTs. Overall, these data reveal mechanisms of emergence of mesenchyme from endocardium or epicardium at single-cell resolution and will serve as an atlas of EMT initiation and progression with broad implications in regenerative medicine and cancer biology.

Suggested Citation

  • Jeremy Lotto & Rebecca Cullum & Sibyl Drissler & Martin Arostegui & Victoria C. Garside & Bettina M. Fuglerud & Makenna Clement-Ranney & Avinash Thakur & T. Michael Underhill & Pamela A. Hoodless, 2023. "Cell diversity and plasticity during atrioventricular heart valve EMTs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41279-6
    DOI: 10.1038/s41467-023-41279-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41279-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41279-6?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. Sonja Nowotschin & Manu Setty & Ying-Yi Kuo & Vincent Liu & Vidur Garg & Roshan Sharma & Claire S. Simon & Nestor Saiz & Rui Gardner & Stéphane C. Boutet & Deanna M. Church & Pamela A. Hoodless & Anna, 2019. "The emergent landscape of the mouse gut endoderm at single-cell resolution," Nature, Nature, vol. 569(7756), pages 361-367, May.
    2. Blanca Pijuan-Sala & Jonathan A. Griffiths & Carolina Guibentif & Tom W. Hiscock & Wajid Jawaid & Fernando J. Calero-Nieto & Carla Mulas & Ximena Ibarra-Soria & Richard C. V. Tyser & Debbie Lee Lian H, 2019. "A single-cell molecular map of mouse gastrulation and early organogenesis," Nature, Nature, vol. 566(7745), pages 490-495, February.
    3. Pearl Quijada & Michael A. Trembley & Adwiteeya Misra & Jacquelyn A. Myers & Cameron D. Baker & Marta Pérez-Hernández & Jason R. Myers & Ronald A. Dirkx & Ethan David Cohen & Mario Delmar & John M. As, 2021. "Coordination of endothelial cell positioning and fate specification by the epicardium," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    4. T. Yvanka de Soysa & Sanjeev S. Ranade & Satoshi Okawa & Srikanth Ravichandran & Yu Huang & Hazel T. Salunga & Amelia Schricker & Antonio del Sol & Casey A. Gifford & Deepak Srivastava, 2019. "Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects," Nature, Nature, vol. 572(7767), pages 120-124, August.
    5. Bin Zhou & Qing Ma & Satish Rajagopal & Sean M. Wu & Ibrahim Domian & José Rivera-Feliciano & Dawei Jiang & Alexander von Gise & Sadakatsu Ikeda & Kenneth R. Chien & William T. Pu, 2008. "Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart," Nature, Nature, vol. 454(7200), pages 109-113, July.
    6. Tui Neri & Emilye Hiriart & Patrick P. van Vliet & Emilie Faure & Russell A. Norris & Batoul Farhat & Bernd Jagla & Julie Lefrancois & Yukiko Sugi & Thomas Moore-Morris & Stéphane Zaffran & Randolph S, 2019. "Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    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. Luke Simpson & Andrew Strange & Doris Klisch & Sophie Kraunsoe & Takuya Azami & Daniel Goszczynski & Triet Minh & Benjamin Planells & Nadine Holmes & Fei Sang & Sonal Henson & Matthew Loose & Jennifer, 2024. "A single-cell atlas of pig gastrulation as a resource for comparative embryology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Ran Wang & Xianfa Yang & Jiehui Chen & Lin Zhang & Jonathan A. Griffiths & Guizhong Cui & Yingying Chen & Yun Qian & Guangdun Peng & Jinsong Li & Liantang Wang & John C. Marioni & Patrick P. L. Tam & , 2023. "Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Karin D. Prummel & Helena L. Crowell & Susan Nieuwenhuize & Eline C. Brombacher & Stephan Daetwyler & Charlotte Soneson & Jelena Kresoja-Rakic & Agnese Kocere & Manuel Ronner & Alexander Ernst & Zahra, 2022. "Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    4. Dorota Zawada & Jessica Kornherr & Anna B. Meier & Gianluca Santamaria & Tatjana Dorn & Monika Nowak-Imialek & Daniel Ortmann & Fangfang Zhang & Mark Lachmann & Martina Dreßen & Mariaestela Ortiz & Vi, 2023. "Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Nimrod Rappoport & Elad Chomsky & Takashi Nagano & Charlie Seibert & Yaniv Lubling & Yael Baran & Aviezer Lifshitz & Wing Leung & Zohar Mukamel & Ron Shamir & Peter Fraser & Amos Tanay, 2023. "Single cell Hi-C identifies plastic chromosome conformations underlying the gastrulation enhancer landscape," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Shengyong Yu & Chunhua Zhou & Jiangping He & Zhaokai Yao & Xingnan Huang & Bowen Rong & Hong Zhu & Shijie Wang & Shuyan Chen & Xialian Wang & Baomei Cai & Guoqing Zhao & Yuhan Chen & Lizhan Xiao & He , 2022. "BMP4 drives primed to naïve transition through PGC-like state," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Brian DeVeale & Leqian Liu & Ryan Boileau & Jennifer Swindlehurst-Chan & Bryan Marsh & Jacob W. Freimer & Adam Abate & Robert Blelloch, 2022. "G1/S restriction point coordinates phasic gene expression and cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Ryan J. Smith & Hongpan Zhang & Shengen Shawn Hu & Theodora Yung & Roshane Francis & Lilian Lee & Mark W. Onaitis & Peter B. Dirks & Chongzhi Zang & Tae-Hee Kim, 2022. "Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Javier Rodríguez-Ubreva & Anna Arutyunyan & Marc Jan Bonder & Lucía Del Pino-Molina & Stephen J. Clark & Carlos de la Calle-Fabregat & Luz Garcia-Alonso & Louis-François Handfield & Laura Ciudad & Edu, 2022. "Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    10. Sina Schumacher & Max Fernkorn & Michelle Marten & Rui Chen & Yung Su Kim & Ivan Bedzhov & Christian Schröter, 2024. "Tissue-intrinsic beta-catenin signals antagonize Nodal-driven anterior visceral endoderm differentiation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    11. Ajita Shree & Musale Krushna Pavan & Hamim Zafar, 2023. "scDREAMER for atlas-level integration of single-cell datasets using deep generative model paired with adversarial classifier," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    12. Charles Petitpré & Louis Faure & Phoebe Uhl & Paula Fontanet & Iva Filova & Gabriela Pavlinkova & Igor Adameyko & Saida Hadjab & Francois Lallemend, 2022. "Single-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Mingze Gao & Chen Qiao & Yuanhua Huang, 2022. "UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Allen W. Lynch & Myles Brown & Clifford A. Meyer, 2023. "Multi-batch single-cell comparative atlas construction by deep learning disentanglement," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    15. Jin Ming & Lihui Lin & Jiajun Li & Linlin Wu & Shicai Fang & Tao Huang & Yu Fu & Dong Liu & Wenhui Zhang & Chen Li & Yongzheng Yang & Yi Huang & Yue Qin & Junqi Kuang & Xingnan Huang & Liman Guo & Xia, 2024. "Cell fate decision by a morphogen-transcription factor-chromatin modifier axis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    16. C. Biben & T. S. Weber & K. S. Potts & J. Choi & D. C. Miles & A. Carmagnac & T. Sargeant & C. A. Graaf & K. A. Fennell & A. Farley & O. J. Stonehouse & M. A. Dawson & D. J. Hilton & S. H. Naik & S. T, 2023. "In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    17. Zeyang Wang & Rui Fan & Angela Russo & Filippo M. Cernilogar & Alexander Nuber & Silvia Schirge & Irina Shcherbakova & Iva Dzhilyanova & Enes Ugur & Tobias Anton & Lisa Richter & Heinrich Leonhardt & , 2022. "Dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    18. Norika Liu & Naofumi Kawahira & Yasuhiro Nakashima & Haruko Nakano & Akiyasu Iwase & Yasunobu Uchijima & Mei Wang & Sean M. Wu & Susumu Minamisawa & Hiroki Kurihara & Atsushi Nakano, 2023. "Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Monika Graf & Marta Interlandi & Natalia Moreno & Dörthe Holdhof & Carolin Göbel & Viktoria Melcher & Julius Mertins & Thomas K. Albert & Dennis Kastrati & Amelie Alfert & Till Holsten & Flavia de Far, 2022. "Single-cell transcriptomics identifies potential cells of origin of MYC rhabdoid tumors," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    20. Nicolas Allègre & Sabine Chauveau & Cynthia Dennis & Yoan Renaud & Dimitri Meistermann & Lorena Valverde Estrella & Pierre Pouchin & Michel Cohen-Tannoudji & Laurent David & Claire Chazaud, 2022. "NANOG initiates epiblast fate through the coordination of pluripotency genes expression," Nature Communications, Nature, vol. 13(1), pages 1-13, 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:14:y:2023:i:1:d:10.1038_s41467-023-41279-6. 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.