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.
Development of microbial communities is a complex multiscale phenomenon with wide-ranging biomedical and ecological implications. How biological and physical processes determine emergent spatial structures in microbial communities remains poorly understood due to a lack of simultaneous measurements of gene expression and cellular behaviour in space and time. Here we combined live-cell microscopy with a robotic arm for spatiotemporal sampling, which enabled us to simultaneously acquire phenotypic imaging data and spatiotemporal transcriptomes during
- PAR ID:
- 10526110
- Publisher / Repository:
- MacMillan
- Date Published:
- Journal Name:
- Nature Microbiology
- Volume:
- 8
- Issue:
- 12
- ISSN:
- 2058-5276
- Page Range / eLocation ID:
- 2378 to 2391
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Background Gene duplication events are critical for the evolution of new gene functions. Aristaless is a major regulator of distinct developmental processes. It is most known for its role during appendage development across animals. However, more recently other distinct biological functions have been described for this gene and its duplicates. Butterflies and moths have two copies of
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Conclusions Overall, our data suggest that while both gene copies play a role in embryogenesis and wing pigmentation, the duplicates have diverged temporally and mechanistically across those functions. Our study helps clarify principles behind sub-functionalization and gene expression evolution associated with developmental functions following gene duplication events.
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