A cell atlas of the developing human lung has identified 144 cell states in the early stages of life – and uncovered new links between developmental cells and lung cancer.
The study is part of the Human Cell Atlas and researchers at the Wellcome Sanger Institute, EMBL’s European Bioinformatics Institute (EMBL-EBI), the Gurdon Institute at the University of Cambridge, and collaborators, examined which genes are activated in different stages of lung development.
Combining this with spatial technologies, which pinpoint the exact location of cells, they have created the Developmental Lung Cell Atlas, which is published in the latest edition of Cell.
The highly detailed atlas is a guidebook on healthy lung development and can be used as a baseline to investigate how lung diseases originate.
The researchers identified 144 cell types, such as intermediate and transitional cell types, including a subtype that could be linked to the development of human small cell lung cancer later in life.
They used the atlas to make predictions about how lung cells develop, especially which genes are the key players driving this process and used organoid models to validate the emerging hypotheses.
This, they said, demonstrated the atlas can be used to accurately predict the stages and cells involved in tissue development.
Co-first author Dr Peng He, from the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute (EMBL-EBI), said: “Our high-resolution computational analysis has identified previously undescribed and rare populations in the developing human lung.
“In these new populations, we found one that is associated with a poorly understood type of small lung cell cancer in adults. While further research is required to understand the link, this shows the important insights into mechanisms shared by development and disease that can be found using our unique cell atlas.
“In addition to this, by including chromatin accessibility data and in vitro perturbation experiments, our work shows how key transcription factors can individually dictate lineage choices, allowing us to start to understand the regulatory logic that controls differentiation pathways.”
Dr Kerstin Meyer, co-senior author from the Wellcome Sanger Institute, added: “By documenting cells that are fleeting and not found in adult lungs, it enables us to see how cells differentiate in detail that has not previously been possible. If we are to fully understand the root causes of disease, we require a complete view of cells at all stages in the human body, and this atlas helps us to do that.”
Peng H, Kyungtae L, Dawei S et al. A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates. Cell 8 December 2022
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