First 3D nanoscale maps of human airway epithelium reveal hidden architecture of lung defense cells
Researchers at Queen Mary University of London and University of Cambridge in collaboration with colleagues at HHMI Janelia and NIH, have created some of the most detailed three-dimensional maps ever generated of human airway cells, revealing how the specialized cells that protect our lungs are built and organized.
The study, published in Cell Reports, combines advanced volume electron microscopy with super-resolution light microscopy to reconstruct individual airway cells in three dimensions at nanometer resolution. The work provides an unprecedented view of how the internal structures of human cells are organized as airway cells mature and acquire specialized functions.
"Our understanding of cells has traditionally relied on looking at thin 2D slices or individual molecular components," said Dr. Vito Mennella, Reader in Nanoscale Biology at Queen Mary University of London and senior author of the study. "By reconstructing complete cells in three dimensions, we can now see how the different parts of a cell are arranged and connected, providing a much more complete and time-resolved picture of how human tissues are made and function."
The nanoscale maps have the potential to provide a better understanding of respiratory diseases. Many lung diseases, such as asthma, chronic bronchitis and chronic obstructive pulmonary disease, involve changes or damage to airway cells. By comparing diseased cells with these healthy reference maps, researchers could pinpoint exactly what changes occur, revealing early warning signs and mechanisms of disease and providing new treatment targets.
A new way to see human cells
The airway epithelium, the thin layer of cells that line the inside surface of the respiratory tract, forms the first line of defense against the external environment, continuously protecting the lungs from inhaled particles, pathogens and pollutants. To perform this role, airway cells undergo a highly organized process of differentiation, developing specialized structures including motile cilia—the microscopic, hair-like structures that extend from the surface of certain cells—which help clear material from the respiratory tract.
Until now, it has not been possible to follow this process, capturing the complete three-dimensional organization of the cell and its internal components. The researchers combined large-scale three-dimensional volume electron microscopy with AI-based segmentation, super-resolution microscopy and CRISPR-Cas9 KO approaches, allowing them to connect information across different biological scales—from entire cells and organelles down to the function of specific molecular structures.
This multimodal approach revealed unexpected complexity and plasticity in the architecture of airway cells and uncovered previously unrecognized relationships and physical contacts between cellular structures involved in building and maintaining the machinery required for airway defense.
A publicly available resource for the scientific community
A key outcome of the study is the creation of an openly accessible digital resource generated in collaboration with the enhanced FIB-SEM imaging shared resource at HHMI Janelia. The resulting nanoscale datasets will be made available to researchers worldwide through the CellMap initiative, supporting broader exploration and reuse by the scientific community. The datasets will also be linked with the LungMAP and the EMBL-EBI Cell Ontology efforts, allowing these nanoscale maps to be integrated with existing molecular and cellular reference resources.
"These are not simply images—they are detailed digital representations of human cells that can be explored, analyzed and reused by scientists around the world," said Mennella. "By making these resources openly available, we hope to accelerate discoveries in lung biology, respiratory disease and the development of new computational approaches for studying human cells."
Implications for human health
Understanding how healthy airway cells are assembled provides an essential reference point for investigating diseases where these structures become disrupted, including asthma, chronic obstructive pulmonary disease (COPD) and inherited disorders affecting cilia function. "Our lab is currently involved in a major nanopathology effort aimed at understanding how chronic respiratory diseases change the single-cell biology of the airway to identify new therapeutic targets," said Mennella.
The study also demonstrates how advances in imaging, computational biology and artificial intelligence are transforming biomedical research. Large-scale cellular maps such as these could provide the foundation for future AI-driven approaches to understand human biology and predict how cells respond to disease or treatment.
By contributing detailed nanoscale reconstructions of human airway cells, this work represents a step toward a future where researchers can navigate the complexity of human tissues with the same precision that modern maps allow us to explore the world around us.
Volume electron microscopy
Volume electron microscopy (volume EM) enables scientists to create high-resolution 3D images of cells and tissues at a scale that was previously impossible. It is one of the most promising technologies to watch because it overcomes the limitations of traditional electron microscopy, providing unprecedented insights into diseases such as cancer and enabling ambitious projects like mapping the brain in extraordinary detail.
Publication details
Aaran Vijayakumaran et al, 3D nanoscale reconstruction of human airway multiciliogenesis reveals cellular architecture remodeling and cilia-mitochondria link via rootlets, Cell Reports (2026). DOI: 10.1016/j.celrep.2026.117714
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Citation: First 3D nanoscale maps of human airway epithelium reveal hidden architecture of lung defense cells (2026, July 23) retrieved 23 July 2026 from https://phys.org/news/2026-07-3d-nanoscale-human-airway-epithelium.html
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