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The human lung mapped in unprecedented detail

The most comprehensive cellular map of the human lung has been published in Nature Medicine. It is part of the Human Cell Atlas (HCA) initiative and provides insights into lung cell diversity and disease-associated changes.

Mapping a lung

Given the variety of pathogens that target lung tissue, understanding the cellular makeup of the human lung has been a priority for researchers. However, individual studies that sequence lung tissue at single cell resolution are often under-powered. In the past, researchers had to ask, which dataset is best for my purposes? Now, scientists have the know-how to integrate this data together into one atlas

Using the best performing data integration methods, the researchers here combined data from 49 datasets, over 486 individuals and 2.4 million cells. 14 high quality datasets were initially used to make this map of the lung. Transfer learning and AI were then utilised to incorporate the remaining 35 datasets to complete the extended atlas (Figure 1). This Human Lung Cell Atlas was principally built using data from healthy lungs and found a remarkable 61 distinct cell types.

Figure 1: Overview of the workflow used in this study. Left. The initial data selected to build the HCLA core. Middle. Transfer learning allowed the incorporation of 35 datasets produced previously. Right. The available data from the core and extended atlases including cell types, biomarkers of age/sex etc. and disease state changes. Figure taken from original publication.

In sickness and in health

Beyond unique cell types, the atlas also allowed the researchers to find effects of age, sex, smoking and BMI on specific cells in the human lung. For example, a higher BMI resulted in high inflammatory gene expression in alveolar macrophages reflecting chronic inflammation.

The team also used data from 10 different lung diseases such as COVID-19, lung carcinoma and pulmonary fibrosis. By projecting this disease data onto the healthy data, insights into lung disease states were gathered. For example, multiple diseases saw an increase of lung monocyte-derived macrophages, involved in pulmonary scar formation. “Finding these shared disease-associated cells is really exciting, and reveals a totally different way of looking at lung diseases” stated Professor Martin Nawjin, senior author on the paper.

Better together

This atlas now serves as a reference for all future HCA studies. New lung data can be incorporated and the map itself is available for anyone to explore and gain insights from. Furthermore, the data integration effort documented here is a blueprint for others who wish to create such atlases for other organs.

This was an excellent example of collaborative science. 100 contributors from more than 60 institutions across the world worked directly on this project and data from a variety of other groups were utilised. More human tissues are in the sights of the HCA team and this lung atlas has set the benchmark for that work.

More on these topics

Human Cell / Human Cell Atlas / Lung / Single cell