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Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration

Author

Listed:
  • Yu Xia

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Sierra Duca

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Björn Perder

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Friederike Dündar

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Paul Zumbo

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Miaoyan Qiu

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Jun Yao

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Yingxi Cao

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Michael R. M. Harrison

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Lior Zangi

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Doron Betel

    (Weill Cornell Medical College
    Weill Cornell Medical College
    Weill Cornell Medical College)

  • Jingli Cao

    (Weill Cornell Medical College
    Weill Cornell Medical College)

Abstract

The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we define the epithelial and mesenchymal subsets of the epicardium. We further identify a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by ptx3a and col12a1b expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and pdgfra+hapln1a+ mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reduced nrg1 expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.

Suggested Citation

  • Yu Xia & Sierra Duca & Björn Perder & Friederike Dündar & Paul Zumbo & Miaoyan Qiu & Jun Yao & Yingxi Cao & Michael R. M. Harrison & Lior Zangi & Doron Betel & Jingli Cao, 2022. "Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35433-9
    DOI: 10.1038/s41467-022-35433-9
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    1. Ludo Waltman & Nees Eck, 2013. "A smart local moving algorithm for large-scale modularity-based community detection," The European Physical Journal B: Condensed Matter and Complex Systems, Springer;EDP Sciences, vol. 86(11), pages 1-14, November.
    2. Chris Jopling & Eduard Sleep & Marina Raya & Mercè Martí & Angel Raya & Juan Carlos Izpisúa Belmonte, 2010. "Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation," Nature, Nature, vol. 464(7288), pages 606-609, March.
    3. Madhav Mantri & Gaetano J. Scuderi & Roozbeh Abedini-Nassab & Michael F. Z. Wang & David McKellar & Hao Shi & Benjamin Grodner & Jonathan T. Butcher & Iwijn De Vlaminck, 2021. "Spatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Junyue Cao & Malte Spielmann & Xiaojie Qiu & Xingfan Huang & Daniel M. Ibrahim & Andrew J. Hill & Fan Zhang & Stefan Mundlos & Lena Christiansen & Frank J. Steemers & Cole Trapnell & Jay Shendure, 2019. "The single-cell transcriptional landscape of mammalian organogenesis," Nature, Nature, vol. 566(7745), pages 496-502, February.
    5. Héctor Sánchez-Iranzo & María Galardi-Castilla & Carolina Minguillón & Andrés Sanz-Morejón & Juan Manuel González-Rosa & Anastasia Felker & Alexander Ernst & Gabriela Guzmán-Martínez & Christian Mosim, 2018. "Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    6. Ke Wei & Vahid Serpooshan & Cecilia Hurtado & Marta Diez-Cuñado & Mingming Zhao & Sonomi Maruyama & Wenhong Zhu & Giovanni Fajardo & Michela Noseda & Kazuto Nakamura & Xueying Tian & Qiaozhen Liu & An, 2015. "Epicardial FSTL1 reconstitution regenerates the adult mammalian heart," Nature, Nature, vol. 525(7570), pages 479-485, September.
    7. Daniel Wehner & Themistoklis M. Tsarouchas & Andria Michael & Christa Haase & Gilbert Weidinger & Michell M. Reimer & Thomas Becker & Catherina G. Becker, 2017. "Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
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