Author
Listed:
- Elie N. Farah
(University of California San Diego)
- Robert K. Hu
(University of California San Diego)
- Colin Kern
(University of California San Diego)
- Qingquan Zhang
(University of California San Diego)
- Ting-Yu Lu
(University of California San Diego)
- Qixuan Ma
(University of California San Diego)
- Shaina Tran
(University of California San Diego)
- Bo Zhang
(University of California San Diego
University of California San Diego)
- Daniel Carlin
(University of California San Diego)
- Alexander Monell
(University of California San Diego)
- Andrew P. Blair
(University of California San Diego)
- Zilu Wang
(University of California San Diego)
- Jacqueline Eschbach
(University of California San Diego)
- Bin Li
(University of California San Diego)
- Eugin Destici
(University of California San Diego)
- Bing Ren
(University of California San Diego
University of California San Diego
Ludwig Institute for Cancer Research
University of California San Diego)
- Sylvia M. Evans
(University of California San Diego
University of California San Diego)
- Shaochen Chen
(University of California San Diego
University of California San Diego
University of California San Diego
University of California San Diego)
- Quan Zhu
(University of California San Diego)
- Neil C. Chi
(University of California San Diego
University of California San Diego
University of California San Diego
University of California San Diego)
Abstract
The heart, which is the first organ to develop, is highly dependent on its form to function1,2. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell–cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair.
Suggested Citation
Elie N. Farah & Robert K. Hu & Colin Kern & Qingquan Zhang & Ting-Yu Lu & Qixuan Ma & Shaina Tran & Bo Zhang & Daniel Carlin & Alexander Monell & Andrew P. Blair & Zilu Wang & Jacqueline Eschbach & Bi, 2024.
"Spatially organized cellular communities form the developing human heart,"
Nature, Nature, vol. 627(8005), pages 854-864, March.
Handle:
RePEc:nat:nature:v:627:y:2024:i:8005:d:10.1038_s41586-024-07171-z
DOI: 10.1038/s41586-024-07171-z
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