{ "abstract": "Developmental dynamics involve the specification of diverse cell types and their spatial organization into multicellular niches1. Here we combine single-cell and spatial multiomics to define 21 distinct tissue niches in the developing heart, which we use to develop a context-aware, resolution-agnostic niche classification tool (TissueTypist). Applying high-resolution spatial profiling to the developing sinoatrial node, we resolve three pacemaker cell subtypes arrayed along a linear axis. First trimester subpopulations, such as pacemaker cells in the sinus horn and sinoatrial node head region, display neuroattractant programs and interact with parasympathetic neurons via interactions that include Eph–ephrin and semaphorin–plexin signalling. Temporal trajectories map the maturation of atrial and ventricular cardiomyocytes and uncover a lipid–metabolic switch and potential key regulators of cell-type identity. In the ventricle, we identify cellular and transcriptional gradients along both pseudotime and transmural axes, which provide molecular insights into myocardial compaction and maturation. Comparative profiling revealed that hearts with trisomy 21 are depleted in compact cardiomyocytes and exhibit increased apoptosis relative to euploid hearts. This finding was validated in isogenic-matched trisomy 21 and euploid cardiomyocytes derived from induced pluripotent stem cells. These early developmental perturbations may contribute to the increased risk of congenital heart disease associated with Down’s syndrome. In summary, we present a spatially resolved framework of human cardiac development to enable systematic explorations of developmental niches in health and disease.", "abstract_shown": true, "affiliations": [ "Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK", "Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. kk837@cam.ac.uk", "Department of Medicine, University of Cambridge, Cambridge, UK", "National Heart Lung Institute, Imperial College London, London, UK", "The Francis Crick Institute, London, UK", "Wellcome Sanger Institute, Hinxton, UK", "John van Geest Centre for Brain Repair, Cambridge University, Cambridge, UK", "Cardiac Morphology Unit, Royal Brompton Hospital and Imperial College London, London, UK", "Department of Oncology, University of Cambridge, Cambridge, UK", "Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. ss661@cam.ac.uk", "Department of Medicine, University of Cambridge, Cambridge, UK. ss661@cam.ac.uk", "CIFAR Macmillan Multi-scale Human Programme, CIFAR, Toronto, Ontario, Canada. sat1003@cam.ac.uk", "Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. sat1003@cam.ac.uk", "Department of Medicine, University of Cambridge, Cambridge, UK. sat1003@cam.ac.uk" ], "article_type": "research article", "arxiv": null, "author_total": 37, "authors": [ { "affs": [ 0 ], "name": "James J. Cranley", "orcid": "0000-0002-0408-5801" }, { "affs": [ 1 ], "name": "Kazumasa Kanemaru", "orcid": "0000-0003-0018-8966" }, { "affs": [ 0, 2 ], "name": "Semih Bayraktar", "orcid": "0000-0001-9549-7117" }, { "affs": [ 0, 2 ], "name": "Vincent R. Knight-Schrijver", "orcid": "0000-0002-7916-3827" }, { "affs": [ 3, 4 ], "name": "Rebecca Hulbert", "orcid": "0009-0000-7852-8268" }, { "affs": [ 4 ], "name": "Eva Lana‐Elola", "orcid": "0000-0003-3351-5820" }, { "affs": [ 4 ], "name": "Rifdat Aoidi", "orcid": "0000-0002-0617-0284" }, { "affs": [ 5 ], "name": "J. Patrick Pett", "orcid": "0000-0002-5249-444X" }, { "affs": [ 0 ], "name": "Anna Wilbrey-Clark", "orcid": "0000-0002-5399-7997" }, { "affs": [ 0 ], "name": "Krzysztof Polański", "orcid": "0000-0002-2586-9576" }, { "affs": [ 5 ], "name": "Monika Dabrowska" }, { "affs": [ 5 ], "name": "Ilaria Mulas", "orcid": "0000-0003-2556-9685" }, { "affs": [ 5 ], "name": "Harriet F. Johnson", "orcid": "0000-0003-0075-5297" }, { "affs": [ 0 ], "name": "Noémie Combémorel", "orcid": "0000-0002-9308-1959" }, { "affs": [ 0 ], "name": "Yizhou Yu", "orcid": "0000-0002-4800-9392" }, { "affs": [ 0, 5 ], "name": "Jack A. Palmer", "orcid": "0009-0008-4405-9959" }, { "affs": [ 0 ], "name": "이우찬" }, { "affs": [ 0 ], "name": "Jore Van Wauwe", "orcid": "0000-0003-2969-1805" }, { "affs": [ 0 ], "name": "John-Poul Ng-Blichfeldt", "orcid": "0000-0002-8332-2659" }, { "affs": [ 5 ], "name": "Laura Richardson", "orcid": "0000-0002-8075-3816" }, { "affs": [ 0 ], "name": "Claudia I. Semprich", "orcid": "0000-0002-2446-9028" }, { "affs": [ 0 ], "name": "Rakeshlal Kapuge", "orcid": "0009-0001-3394-0387" }, { "affs": [ 0 ], "name": "Shani Perera", "orcid": "0000-0001-8021-2078" }, { "affs": [ 6 ], "name": "Xiaoling He", "orcid": "0009-0004-1002-8418" }, { "affs": [ 7 ], "name": "Siew Yen Ho", "orcid": "0000-0002-3913-5637" }, { "affs": [ 0 ], "name": "Nadav Yayon", "orcid": "0000-0002-7034-0524" }, { "affs": [ 5 ], "name": "Elizabeth J. Tuck", "orcid": "0000-0002-1837-7549" }, { "affs": [ 5 ], "name": "Kenny Roberts", "orcid": "0000-0001-6155-0821" }, { "affs": [ 0, 5 ], "name": "Hongorzul Davaapil", "orcid": "0000-0001-5947-9317" }, { "affs": [ 0, 5 ], "name": "Laure Gambardella", "orcid": "0000-0001-5771-1565" }, { "affs": [ 0, 8 ], "name": "Anna Philpott", "orcid": "0000-0003-3789-2463" }, { "affs": [ 5 ], "name": "Minal Patel" }, { "affs": [ 0 ], "name": "Richard C. V. Tyser", "orcid": "0000-0001-7884-1756" }, { "affs": [ 3, 4 ], "name": "Andreia Sofia Bernardo", "orcid": "0000-0002-5355-6657" }, { "affs": [ 4 ], "name": "Victor L. J. Tybulewicz", "orcid": "0000-0003-2439-0798" }, { "affs": [ 9, 10 ], "name": "Sanjay Sinha", "orcid": "0000-0001-5900-1209" }, { "affs": [ 11, 12, 13 ], "name": "Sarah Amalia Teichmann", "orcid": "0000-0002-6294-6366" } ], "bibtex": "https://research.draconitic.com/paper/adfced6ff000m.bib", "cited_by": 12, "doi": "10.1038/s41586-026-11125-y", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13716840/", "id": "adfced6ff000m", "issns": [ "0028-0836", "1476-4687" ], "landing_url": "https://doi.org/10.1038/s41586-026-11125-y", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Article" ], [ "openalex", "1312|Congenital heart defects research" ] ], "openalex": "W7212235065", "pdf_url": null, "pmcid": "PMC13716840", "pmid": "42844467", "published": "2026-10-07", "publisher": "Nature Portfolio", "ris": "https://research.draconitic.com/paper/adfced6ff000m.ris", "sources": [ { "first_seen": "2026-11-01T12:24:02Z", "native_id": "PMC13716840", "source": "pmc", "url": "https://doi.org/10.1038/s41586-026-11125-y" }, { "first_seen": "2026-11-04T13:21:06Z", "native_id": "W7212235065", "source": "openalex", "url": "https://doi.org/10.1038/s41586-026-11125-y" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|Congenital heart defects research", "subfield": "molecular-biology" } ], "title": "Dynamics of human cardiogenesis and its disruption in trisomy 21", "title_text": "Dynamics of human cardiogenesis and its disruption in trisomy 21", "type": "peer-reviewed", "updated_at": "2026-11-04T13:21:06Z", "url": "https://research.draconitic.com/paper/adfced6ff000m", "venue": "Nature", "versions": [] }