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

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 () and Ying Su ()
Additional contact information
Lei Li: BGI Research
Meina Lu: Ocean University of China
Lidong Guo: BGI Research
Xuejiao Zhang: Ocean University of China
Qun Liu: BGI Research
Meiling Zhang: Ocean University of China
Junying Gao: Ocean University of China
Mengyang Xu: BGI Research
Yijian Lu: Ocean University of China
Fang Zhang: 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
Nannan Zhang: BGI Research
Wenjie Guo: BGI Research
Tao Yang: BGI Research
Jing Chen: BGI Research
Yating Qin: BGI Research
Zhe Zhang: MGI Tech
Wei Cui: BGI Research
Lindong Yu: Ocean University of China
Ying Gu: BGI Research
Huanming Yang: BGI Research
Xun Xu: BGI Research
Jianxun Wang: Qingdao University
Caroline E. Burns: Boston Children’s Hospital
C. Geoffrey Burns: Boston Children’s Hospital
Kai Han: BGI Research
Long Zhao: Ocean University of China
Guangyi Fan: BGI Research
Ying Su: Ocean University of China

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59070-0

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DOI: 10.1038/s41467-025-59070-0

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