Dynamics of human cardiogenesis and its disruption in trisomy 21

@article{cranley2026dynamics,
  title = {{Dynamics of human cardiogenesis and its disruption in trisomy 21}},
  author = {James J. Cranley and Kazumasa Kanemaru and Semih Bayraktar and Vincent R. Knight-Schrijver and Rebecca Hulbert and Eva Lana‐Elola and Rifdat Aoidi and J. Patrick Pett and Anna Wilbrey-Clark and Krzysztof Polański and Monika Dabrowska and Ilaria Mulas and Harriet F. Johnson and Noémie Combémorel and Yizhou Yu and Jack A. Palmer and 이우찬 and Jore Van Wauwe and John-Poul Ng-Blichfeldt and Laura Richardson and Claudia I. Semprich and Rakeshlal Kapuge and Shani Perera and Xiaoling He and Siew Yen Ho and Nadav Yayon and Elizabeth J. Tuck and Kenny Roberts and Hongorzul Davaapil and Laure Gambardella and Anna Philpott and Minal Patel and Richard C. V. Tyser and Andreia Sofia Bernardo and Victor L. J. Tybulewicz and Sanjay Sinha and Sarah Amalia Teichmann},
  journal = {Nature},
  year = {2026},
  month = oct,
  doi = {10.1038/s41586-026-11125-y},
  url = {https://doi.org/10.1038/s41586-026-11125-y},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Dynamics of human cardiogenesis and its disruption in trisomy 21
AU  - James J. Cranley
AU  - Kazumasa Kanemaru
AU  - Semih Bayraktar
AU  - Vincent R. Knight-Schrijver
AU  - Rebecca Hulbert
AU  - Eva Lana‐Elola
AU  - Rifdat Aoidi
AU  - J. Patrick Pett
AU  - Anna Wilbrey-Clark
AU  - Krzysztof Polański
AU  - Monika Dabrowska
AU  - Ilaria Mulas
AU  - Harriet F. Johnson
AU  - Noémie Combémorel
AU  - Yizhou Yu
AU  - Jack A. Palmer
AU  - 이우찬
AU  - Jore Van Wauwe
AU  - John-Poul Ng-Blichfeldt
AU  - Laura Richardson
AU  - Claudia I. Semprich
AU  - Rakeshlal Kapuge
AU  - Shani Perera
AU  - Xiaoling He
AU  - Siew Yen Ho
AU  - Nadav Yayon
AU  - Elizabeth J. Tuck
AU  - Kenny Roberts
AU  - Hongorzul Davaapil
AU  - Laure Gambardella
AU  - Anna Philpott
AU  - Minal Patel
AU  - Richard C. V. Tyser
AU  - Andreia Sofia Bernardo
AU  - Victor L. J. Tybulewicz
AU  - Sanjay Sinha
AU  - Sarah Amalia Teichmann
PY  - 2026
DA  - 2026/10/07
JO  - Nature
DO  - 10.1038/s41586-026-11125-y
UR  - https://doi.org/10.1038/s41586-026-11125-y
AB  - 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.
SN  - 0028-0836
SN  - 1476-4687
ER  -