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Spatiotemporal gene expression and cellular dynamics of the developing human heart
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.ORCID iD: 0000-0001-8664-7531
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0009-0004-0909-3554
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.ORCID iD: 0000-0002-4350-2524
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.ORCID iD: 0000-0001-6593-3328
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2025 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 57, no 11, p. 2756-2771Article in journal (Refereed) Published
Abstract [en]

Heart development relies on topologically orchestrated cellular transitions and interactions, many of which remain poorly characterized in humans. Here, we combined unbiased spatial and single-cell transcriptomics with imaging-based validation across postconceptional weeks 5.5 to 14 to uncover the molecular landscape of human early cardiogenesis. We present a high-resolution transcriptomic map of the developing human heart, revealing the spatial arrangements of 31 coarse-grained and 72 fine-grained cell states organized into distinct functional niches. Our findings illuminate key insights into the formation of the cardiac pacemaker-conduction system, heart valves and atrial septum, and uncover unexpected diversity among cardiac mesenchymal cells. We also trace the emergence of autonomic innervation and provide the first spatial account of chromaffin cells in the fetal heart. Our study, supported by an open-access spatially centric interactive viewer, offers a unique resource to explore the cellular and molecular blueprint of human heart development, offering links to genetic causes of heart disease.

Place, publisher, year, edition, pages
Springer Nature , 2025. Vol. 57, no 11, p. 2756-2771
National Category
Cell and Molecular Biology Cardiology and Cardiovascular Disease Developmental Biology Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
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URN: urn:nbn:se:kth:diva-372629DOI: 10.1038/s41588-025-02352-6ISI: 001603555000001PubMedID: 41162788Scopus ID: 2-s2.0-105020193592OAI: oai:DiVA.org:kth-372629DiVA, id: diva2:2012924
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QC 20251111

Available from: 2025-11-11 Created: 2025-11-11 Last updated: 2025-11-11Bibliographically approved

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Lázár, EnikőMauron, RaphaëlAndrusivova, ZanetaFoyer, JuliaHe, MengxiaoLarsson, LudvigSariyar, SanemHansen, Jan N.Vicari, MarcoCzarnewski, PauloKäller Lundberg, EmmaLundeberg, Joakim

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Lázár, EnikőMauron, RaphaëlAndrusivova, ZanetaFoyer, JuliaHe, MengxiaoLarsson, LudvigSariyar, SanemHansen, Jan N.Vicari, MarcoCzarnewski, PauloKäller Lundberg, EmmaLundeberg, Joakim
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Gene TechnologyScience for Life Laboratory, SciLifeLabCellular and Clinical Proteomics
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Nature Genetics
Cell and Molecular BiologyCardiology and Cardiovascular DiseaseDevelopmental BiologyMedical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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