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An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart

Author

Listed:
  • Lei Li

    (BGI Research
    BGI Research)

  • Meina Lu

    (Ocean University of China
    Ocean University of China)

  • Lidong Guo

    (BGI Research
    University of Chinese Academy of Sciences)

  • Xuejiao Zhang

    (Ocean University of China
    Ocean University of China)

  • Qun Liu

    (BGI Research
    University of Copenhagen)

  • Meiling Zhang

    (Ocean University of China
    Ocean University of China)

  • Junying Gao

    (Ocean University of China
    Ocean University of China)

  • Mengyang Xu

    (BGI Research
    BGI Research)

  • Yijian Lu

    (Ocean University of China
    Ocean University of China)

  • Fang Zhang

    (Ocean University of China
    Ocean University of China)

  • Yao Li

    (BGI Research)

  • Ruihua Zhang

    (BGI Research)

  • Xiawei Liu

    (BGI Research)

  • Shanshan Pan

    (BGI Research)

  • Xianghui Zhang

    (BGI Research)

  • Zhen Li

    (BGI Research)

  • Yadong Chen

    (BGI Research)

  • Xiaoshan Su

    (BGI Research
    University of Copenhagen)

  • Nannan Zhang

    (BGI Research)

  • Wenjie Guo

    (BGI Research)

  • Tao Yang

    (BGI Research)

  • Jing Chen

    (BGI Research)

  • Yating Qin

    (BGI Research
    University of Copenhagen)

  • Zhe Zhang

    (MGI Tech)

  • Wei Cui

    (BGI Research)

  • Lindong Yu

    (Ocean University of China
    Ocean University of China)

  • Ying Gu

    (BGI Research
    BGI)

  • Huanming Yang

    (BGI Research
    BGI)

  • Xun Xu

    (BGI Research
    BGI)

  • Jianxun Wang

    (Qingdao University)

  • Caroline E. Burns

    (Boston Children’s Hospital
    Harvard Medical School)

  • C. Geoffrey Burns

    (Boston Children’s Hospital
    Harvard Medical School)

  • Kai Han

    (BGI Research
    University of Copenhagen)

  • Long Zhao

    (Ocean University of China
    Ocean University of China)

  • Guangyi Fan

    (BGI Research
    BGI Research
    BGI Research
    BGI Research)

  • Ying Su

    (Ocean University of China
    Ocean University of China)

Abstract

Adult zebrafish robustly regenerate injured hearts through a complex orchestration of molecular and cellular activities. However, this remarkable process, which is largely non-existent in humans, remains incompletely understood. Here, we utilize integrated spatial transcriptomics (Stereo-seq) and single-cell RNA-sequencing (scRNA-seq) to generate a spatially-resolved molecular and cellular atlas of regenerating zebrafish heart across eight stages. We characterize the cascade of cardiomyocyte cell states responsible for producing regenerated myocardium and explore a potential role for tpm4a in cardiomyocyte re-differentiation. Moreover, we uncover the activation of ifrd1 and atp6ap2 genes as a unique feature of regenerative hearts. Lastly, we reconstruct a 4D “virtual regenerating heart” comprising 569,896 cells/spots derived from 36 scRNA-seq libraries and 224 Stereo-seq slices. Our comprehensive atlas serves as a valuable resource to the cardiovascular and regeneration scientific communities and their ongoing efforts to understand the molecular and cellular mechanisms underlying vertebrate heart regeneration.

Suggested Citation

  • Lei Li & Meina Lu & Lidong Guo & Xuejiao Zhang & Qun Liu & Meiling Zhang & Junying Gao & Mengyang Xu & Yijian Lu & Fang Zhang & Yao Li & Ruihua Zhang & Xiawei Liu & Shanshan Pan & Xianghui Zhang & Zhe, 2025. "An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59070-0
    DOI: 10.1038/s41467-025-59070-0
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