An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart
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.
Authors
- Shanshan Pan (ORCID: https://orcid.org/0000-0001-5977-4914)
- Huanming Yang (ORCID: https://orcid.org/0000-0002-0858-3410)
- Long Zhao (ORCID: https://orcid.org/0000-0003-2691-7055)
- Yating Qin (ORCID: https://orcid.org/0000-0001-8024-3210)
- Mengyang Xu (ORCID: https://orcid.org/0000-0002-4487-7088)
- Zhen Li (ORCID: https://orcid.org/0000-0003-0338-8496)
- Guangyi Fan (ORCID: https://orcid.org/0000-0001-7365-1590)
- Xianghui Zhang (ORCID: https://orcid.org/0000-0002-7970-8743)
- Xiaoshan Su (ORCID: https://orcid.org/0000-0003-1734-4208)
- Ying Gu (ORCID: https://orcid.org/0000-0001-7822-0570)
- C. Geoffrey Burns (ORCID: https://orcid.org/0000-0002-5812-6621)
- Caroline E. Burns (ORCID: https://orcid.org/0000-0003-1565-7489)
- Yijian Lu
- Jianxun Wang (ORCID: https://orcid.org/0000-0002-3731-6514)
- Tao Yang (ORCID: https://orcid.org/0000-0003-4211-5183)
- Fang Zhang (ORCID: https://orcid.org/0000-0001-8166-9651)
- Yao Li (ORCID: https://orcid.org/0000-0002-5248-3249)
- Meiling Zhang (ORCID: https://orcid.org/0000-0002-8882-2564)
- Qun Liu (ORCID: https://orcid.org/0000-0003-0548-203X)
- Lei Li (ORCID: https://orcid.org/0000-0001-5478-5681)
- Xun Xu (ORCID: https://orcid.org/0000-0002-5338-5173)
- Nannan Zhang (ORCID: https://orcid.org/0000-0003-0582-8934)
- Ruihua Zhang (ORCID: https://orcid.org/0000-0002-8672-9673)
- Wei Cui (ORCID: https://orcid.org/0000-0001-5885-1068)
- Meina Lu
- Zhe Zhang (ORCID: https://orcid.org/0000-0001-9912-9530)
- Kai Han (ORCID: https://orcid.org/0000-0002-3061-1895)
- Ying Su (ORCID: https://orcid.org/0000-0002-8466-0043)
- Xuejiao Zhang (ORCID: https://orcid.org/0000-0001-9544-0073)
- Yadong Chen (ORCID: https://orcid.org/0000-0003-1945-5403)
- Jing Chen (ORCID: https://orcid.org/0000-0003-1894-335X)
- Lidong Guo (ORCID: https://orcid.org/0000-0003-2520-4416)
- Lindong Yu (ORCID: https://orcid.org/0009-0003-6078-0301)
- Junying Gao
- Xiawei Liu
- Wenjie Guo (ORCID: https://orcid.org/0009-0002-7735-6729)
Institutions
- BGI Group (China) (CN)
- Qingdao University (CN)
- University of Copenhagen (DK)
- Boston Children's Hospital (US)
- Harvard University (US)
- China National GeneBank (CN)
- University of Chinese Academy of Sciences (CN)
- BGI Research (CN)
- Ocean University of China (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-19
- DOI
- https://doi.org/10.1038/s41467-025-59070-0
- Citations
- 21
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 16.12
Funders
- National Natural Science Foundation of China
- Tsinghua University
- Ocean University of China
- Peking University