Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts
Abstract
Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multi-omics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise “add-on” approach as a universal evolutionary strategy. The proto-heart is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. Together, this work establishes a resource for understanding the intrinsic mechanisms of heart evolution.
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Information & Authors
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Published In
Science
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Copyright
Copyright © 2026 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Article versions
Submission history
Received: 21 January 2025
Resubmitted: 29 December 2025
Accepted: 6 July 2026
Acknowledgments
We thank Dr. Zhenlong Wang (Zhengzhou University) for providing zebra finch, Dr. Xufeng Qi (Jinan University) for providing tropical clawed frog, Dr. Zhan Gao (Ocean University of China) for providing amphioxus, Dr. Haijuan Liu (Guangxi Academy of Marine Sciences) for providing horseshoe crab. Dr. Ling Lu (Ocean University of China) for providing the decompression chamber. We are grateful to Dr. Michael Levine (Princeton University), Dr. Lionel Christiaen (University of Bergen), Dr. Kai He (Guangzhou University), Dr. Jing-Wei Xiong (Nanchang University), Dr. Lingling Chen (Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences), Dr. Wen Wang (Northwestern Polytechnical University), Dr. Kun Wang (Northwestern Polytechnical University), Dr. Dan Larhammar (Uppsala University), and Dr. Samuel H. Church (New York University) for their extensive discussions and feedback. We acknowledge the support of the High-Performance Biological Supercomputing Center and core facilities in Institute of Evolution & Marine Biodiversity (IEMB) at the Ocean University of China for this research, and China National GenBank (CNGB).
Funding:
Laoshan Laboratory (LSKJ202203204 to L.Z); The National Key R&D Program of China (2023YFA1800600 to J.-F.F); The National Natural Science Foundation of China (32130107 to S.W.; 32170541 and 31970506 to L.Z.; 32270870 to W.W.; 31970475 and 32170832 to YS.; 32441089 to L.B.; 32222085 to Y.L.; 32422088 to J.W.; 82471753 to Q.L.; 3240210275 to N.H.); The National Key R&D Program of China (2021YFA0805000 to J.-F.F); Guangdong Provincial Genomics Data Center (2021B1212100001 to G.F.); Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (JYB2025XDXIM801); The Fundamental Research Funds for Central Universities China (202012004 to L.Z; 862101225004 to W.W.; 202562018 to L.L.Z.); Beijing Natural Science Foundation (L232088); The State Key Laboratory of Medical Proteomics (SKLP-O202513); Major Program for the Fundamental Research of the Natural Science Foundation of Shandong Province (ZR2025ZD06); Shandong Provincial Natural Science Fund for Distinguished Young Scientists Fund Program (ZR2024JQ022); Key R&D Project of Shandong Province (2021ZLGX03; 2022ZLGX01); Science & Technology Innovation Project of Laoshan Laboratory (LSKJ202203001); Blue Seed Industry Science and Technology Innovation Project (QDLYY-2024011); Outstanding Talent Team Project of Hainan Province (HNYT20240001); PI Project of Southern Marine Science and Engineering Guangdong Laboratory (GML20220018); Young Elite Scientists Sponsorship Program by CAST (2023QNRC001 to W.H.); Taishan Scholar Project Fund of Shandong Province of China.
Author Contributions:
Conceptualization and Funding acquisition: L.Z., G.F., W.W., S.W., J.F.F., S.L.P.; Resources/sample collection and preprocessing: S.L., M.L., X.Z., S.L.P., Y.S., F.Z., P.Z., Y.H.Z., Z.Q., Y.F.L., N.H., X.C., Y.R.L., Y.X.L., L.J., Y.P., Y.Q., S.G., J.Z., W.B.L., M.Z.; scRNA-seq experiments: S.S.P., Y.D.C., Q.S., J.S., Y.R.L.; stereo-seq experiments: X.L., R.L., X.Y.; Genome annotation and orthogroup assignment: W.H.; Software/Computational analysis: S.L., M.L., Q.L., W.H., Y.X.L., J.L., Y.R.L., J.W., R.Z., Y.Z., Y.L.L., Lei L., R.H.Z.; Database construction: L.G., T.Y., J.C., Ling L.; Investigation: X.Z., M.L., Y.F.L., Y.C., Y.R.L., X.D., P.W., S.Q.Y., N.T.; Experiment supervision: L.Z., W.W., S.L., J.F.F., Y.Zhao, J.X.W., H.L.; Data interpretation: L.Z., S.W., W.W., S.L., J.F.F., L.B., L.L.Z.; Visualization: S.L., M.L., Q.L., X.Z., W.H., Y.X.L., J.L.; Writing – original draft: W.W., S.L., M.L., S.W., L.Z., Y.S., W.H., G.F., J.F.F., S.L.P., Q.L., J.L., Y.X.L.; Writing – review & editing: L.Z., W.W., S.W., S.L., J.F.F., M.L., S.L.P., G.F., Y.S., Q.L., R.K., C.G.B., C.E.B., Y.G., X.X., H.Y., Z.B.
Competing Interests:
The authors declare no competing interests.
Data, Code, and Materials Availability:
All raw data generated by bulkRNA-seq, scRNA-seq and Stereo-seq have been deposited to CNGB Nucleotide Sequence Archive: CNP0006537. Additional data, including processed data generated by scRNA-seq and Stereo-seq, associated analysis protocols and software in this study can be accessed from https://db.genomics.cn/stomics/heart/. The published scRNA-seq data of human are available in https://www.ebi.ac.uk/ena/browser/view/ERP123138. The data analysis scripts are available to download at GitHub (https://github.com/ouclian/EvoHeart) and Zenodo (105). The published scRNA-seq and Stereo-seq data of zebrafish are available in the NCBI database under accession number PRJNA1233465. All additional information required to reanalyze the data reported in this paper is available in the supplementary materials or public repositories. Requests for further information can be directed to the lead contact. All materials used in this study are available upon request. Requests should be directed to corresponding author L.Z.
License Information:
Copyright © 2026 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. https://www.science.org/about/science-licenses-journal-article-reuse
Authors
Funding Information
the National Natural Science Foundation of China: 32170541
the National Natural Science Foundation of China: 31970506
the National Natural Science Foundation of China: 32270870
the National Natural Science Foundation of China: 32130107
the National Natural Science Foundation of China: 31970475
the National Natural Science Foundation of China: 32170832
the National Natural Science Foundation of China: 32441089
the National Natural Science Foundation of China: 32222085
the National Natural Science Foundation of China: 32422088
Major Program for the Fundamental Research of the Natural Science Foundation of Shandong Province: ZR2025ZD06
Shandong Provincial Natural Science Fund for Distinguished Young Scientists Fund Program: ZR2024JQ022
Key R&D Project of Shandong Province: 2021ZLGX03; 2022ZLGX01
Science & Technology Innovation Project of Laoshan Laboratory: LSKJ202203001
Blue Seed Industry Science and Technology Innovation Project: QDLYY-2024011
PI Project of Southern Marine Science and Engineering Guangdong Laboratory: GML20220018
Young Elite Scientists Sponsorship Program by CAST: 2023QNRC001
Laoshan Laboratory: LSKJ202203204
the Fundamental Research Funds for Central Universities, China: 202012004
the State Key Laboratory of Medical Proteomics: SKLP-O202513
the Fundamental Research Funds for Central Universities, China: 862101225004
the Fundamental Research Funds for Central Universities, China: 202562018
the National Natural Science Foundation of China: NSFC82471753
Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China: JYB2025XDXM801
the National Key R&D Program of China: 2023YFA1800600
the National Key R&D Program of China: the National Key R&D Program of China
Guangdong Provincial Genomics Data Center: 2021B1212100001
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