Multi-modal refinement of the human heart atlas during the first gestational trimester
Forty first-trimester human hearts were studied to lay groundwork for further studies of the mechanisms underlying congenital heart defects. We first sampled 49,227 cardiac nuclei from three fetuses at 8.6, 9.0, and 10.7 post-conceptional weeks (pcw) for single-nucleus RNA sequencing, enabling the distinction of six classes comprising 21 cell types. Improved resolution led to the identification of previously unappreciated cardiomyocyte populations and minority autonomic and lymphatic endothelial transcriptomes, among others. After integration with 5-7 pcw heart single-cell RNA-sequencing data, we identified a human cardiomyofibroblast progenitor preceding the diversification of cardiomyocyte and stromal lineages. Spatial transcriptomic analysis (six Visium sections from two additional hearts) was aided by deconvolution, and key spatial markers validated on sectioned and whole hearts in two- and three-dimensional space and over time. Altogether, anatomical-positional features, including innervation, conduction and subdomains of the atrioventricular septum, translate latent molecular identity into specialized cardiac functions. This atlas adds unprecedented spatial and temporal resolution to the characterization of human-specific aspects of early heart formation.
Authors
- Sevda Rafatov (ORCID: https://orcid.org/0000-0002-5738-731X)
- Mathias Moreno (ORCID: https://orcid.org/0000-0002-7057-0063)
- Chantal Missirian (ORCID: https://orcid.org/0000-0002-4748-348X)
- Yichi Xu (ORCID: https://orcid.org/0000-0002-8163-3920)
- Marine Herbane (ORCID: https://orcid.org/0009-0004-0387-7315)
- Ivo Vanzetta (ORCID: https://orcid.org/0000-0003-3294-0809)
- Yorick Gitton (ORCID: https://orcid.org/0000-0002-6808-6010)
- Alberto Lombardini
- Alain Chédotal (ORCID: https://orcid.org/0000-0001-7577-3794)
- Christopher De Bono (ORCID: https://orcid.org/0000-0002-4330-7155)
- Heather Etchevers (ORCID: https://orcid.org/0000-0003-0201-3799)
- Séverine Mazaud‐Guittot (ORCID: https://orcid.org/0000-0003-0566-4124)
- Stéphane Zaffran (ORCID: https://orcid.org/0000-0002-0811-418X)
- Samina Kausar (ORCID: https://orcid.org/0000-0002-5207-7136)
- Anaı̈s Baudot (ORCID: https://orcid.org/0000-0003-0885-7933)
- Weiyang Shi (ORCID: https://orcid.org/0000-0001-7678-2131)
- Camille Humbert
Institutions
- Centre National de la Recherche Scientifique (FR)
- Shanghai Medical College of Fudan University (CN)
- Institut de la Vision (FR)
- Inserm (FR)
- École des Hautes Études en Santé Publique (FR)
- Shanghai Jiao Tong University (CN)
- Aix-Marseille Université (FR)
- Fudan University (CN)
- Renji Hospital (CN)
- Sorbonne Université (FR)
- Assistance Publique Hôpitaux de Marseille (FR)
- Institut de Recherche en Santé, Environnement et Travail (FR)
- Institut de Neurosciences de la Timone (FR)
- Centre de Génétique Médicale de Marseille (FR)
Publication Details
- Journal
- Development
- Published
- 2025-02-10
- DOI
- https://doi.org/10.1242/dev.204555
- Citations
- 7
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale