An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart
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-se...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59070-0 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lei Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0802daa8355c432b9da263e1b604438b |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0802daa8355c432b9da263e1b604438b2025-08-20T02:28:09ZengNature PortfolioNature Communications2041-17232025-04-0116112010.1038/s41467-025-59070-0An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heartLei Li0Meina Lu1Lidong Guo2Xuejiao Zhang3Qun Liu4Meiling Zhang5Junying Gao6Mengyang Xu7Yijian Lu8Fang Zhang9Yao Li10Ruihua Zhang11Xiawei Liu12Shanshan Pan13Xianghui Zhang14Zhen Li15Yadong Chen16Xiaoshan Su17Nannan Zhang18Wenjie Guo19Tao Yang20Jing Chen21Yating Qin22Zhe Zhang23Wei Cui24Lindong Yu25Ying Gu26Huanming Yang27Xun Xu28Jianxun Wang29Caroline E. Burns30C. Geoffrey Burns31Kai Han32Long Zhao33Guangyi Fan34Ying Su35Qingdao Key Laboratory of Marine Genomics, BGI ResearchKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaQingdao Key Laboratory of Marine Genomics, BGI ResearchKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaQingdao Key Laboratory of Marine Genomics, BGI ResearchKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaQingdao Key Laboratory of Marine Genomics, BGI ResearchKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchChina National GeneBank, BGI ResearchChina National GeneBank, BGI ResearchQingdao Key Laboratory of Marine Genomics, BGI ResearchMGI TechQingdao Key Laboratory of Marine Genomics, BGI ResearchKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaState Key Laboratory of Genome and Multi-omics Technologies, BGI ResearchState Key Laboratory of Genome and Multi-omics Technologies, BGI ResearchState Key Laboratory of Genome and Multi-omics Technologies, BGI ResearchSchool of Basic Medicine, Qingdao UniversityDivision of Basic and Translational Cardiovascular Research, Department of Cardiology, Boston Children’s HospitalDivision of Basic and Translational Cardiovascular Research, Department of Cardiology, Boston Children’s HospitalQingdao Key Laboratory of Marine Genomics, BGI ResearchKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaQingdao Key Laboratory of Marine Genomics, BGI ResearchKey Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of ChinaAbstract 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.https://doi.org/10.1038/s41467-025-59070-0 |
| spellingShingle | 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 An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart Nature Communications |
| title | An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart |
| title_full | An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart |
| title_fullStr | An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart |
| title_full_unstemmed | An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart |
| title_short | An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart |
| title_sort | organ wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart |
| url | https://doi.org/10.1038/s41467-025-59070-0 |
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