Spatiotemporal gene expression and cellular dynamics of the developing human heart
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.
Authors
- Mats F. Nilsson (ORCID: https://orcid.org/0000-0001-9985-0387)
- Christer Sylvén (ORCID: https://orcid.org/0000-0003-1017-7849)
- Christophe Avenel (ORCID: https://orcid.org/0000-0002-1835-921X)
- Emelie Braun (ORCID: https://orcid.org/0000-0002-4485-6308)
- Mengxiao He (ORCID: https://orcid.org/0000-0001-5905-8467)
- Sergio Marco Salas (ORCID: https://orcid.org/0000-0002-4636-0322)
- Žaneta Andrusivová (ORCID: https://orcid.org/0000-0002-4350-2524)
- Enikő Lázár (ORCID: https://orcid.org/0000-0001-8664-7531)
- Olaf Bergmann (ORCID: https://orcid.org/0000-0003-1065-4107)
- Julia Foyer (ORCID: https://orcid.org/0000-0001-6593-3328)
- Emma K. Lundberg (ORCID: https://orcid.org/0000-0001-7034-0850)
- Joakim Lundeberg (ORCID: https://orcid.org/0000-0003-4313-1601)
- Paulo Czarnewski (ORCID: https://orcid.org/0000-0001-8150-4021)
- Jan N. Hansen (ORCID: https://orcid.org/0000-0002-0489-7535)
- Igor I. Adameyko (ORCID: https://orcid.org/0000-0001-5471-0356)
- Ludvig Larsson (ORCID: https://orcid.org/0000-0003-4209-2911)
- Marco Vicari (ORCID: https://orcid.org/0000-0002-3042-6278)
- Sten Linnarsson (ORCID: https://orcid.org/0000-0002-3491-3444)
- Sanem Sarıyar (ORCID: https://orcid.org/0000-0003-0735-5595)
- Erik Sundström (ORCID: https://orcid.org/0000-0003-2931-8015)
- Raphaël Mauron (ORCID: https://orcid.org/0009-0004-0909-3554)
- Xiaofei Li (ORCID: https://orcid.org/0000-0002-9991-7534)
- Nick Shakari (ORCID: https://orcid.org/0009-0003-2192-769X)
Institutions
- Stockholm University (SE)
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
- Universitätsmedizin Göttingen (DE)
- Chan Zuckerberg Initiative (United States) (US)
- German Centre for Cardiovascular Research (DE)
- University of Göttingen (DE)
- Medical University of Vienna (AT)
- KTH Royal Institute of Technology (SE)
- Stanford University (US)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-10-29
- DOI
- https://doi.org/10.1038/s41588-025-02352-6
- Citations
- 8
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 6.45