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<p>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 <i>tpm4a</i> in cardiomyocyte re-differentiation. Moreover, we uncover the activation of <i>ifrd1</i> and <i>atp6ap2</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月19日

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  • 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,
  • Zhen Li,
  • Yadong Chen,
  • Xiaoshan Su,
  • Nannan Zhang,
  • Wenjie Guo,
  • Tao Yang,
  • Jing Chen,
  • Yating Qin,
  • Zhe Zhang,
  • Wei Cui,
  • Lindong Yu,
  • Ying Gu,
  • Huanming Yang,
  • Xun Xu,
  • Jianxun Wang,
  • Caroline E. Burns,
  • C. Geoffrey Burns,
  • Kai Han,
  • Long Zhao,
  • Guangyi Fan,
  • Ying Su

摘要

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.