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Researchers use single-cell and spatial-omics to create a detailed atlas of human lung development

In a recent paper published in Cell, researchers at the Wellcome Sanger Institute, EMBL’s European Bioinformatics Institute, the Gurdon Institute at the University of Cambridge, and others have collaborated to create “The Developmental Lung Cell Atlas” using single-cell sequencing and spatial-omics technology. This first-of-its-kind multi-omic atlas comprehensively maps human lung development over time and could become an invaluable new resource for researchers studying lung disease.

Building the atlas

Researchers combined single-cell RNA and ATAC sequencing with high-throughput spatial transcriptomics and single-cell imaging to comprehensively map lung development from 5-22 post-conception weeks (pcw). They identified 144 cell types, including previously uncharacterized progenitor cell states, transition populations and a neuroendocrine cell subtype that could be linked to the development of human small-cell lung cancer (SCLC). The researchers also used the atlas to make predictions about progenitor cell states, signalling interactions and lineage-defining transcription factors. They used organoid models to validate these predictions, thus demonstrating that the atlas can be used to predict tissue development accurately, including the stages and the cells involved in these processes.

Dr Kerstin Meyer, co-senior author from the Wellcome Sanger Institute, said: “Our cutting edge single-cell study provides a comprehensive and exceptionally high-quality dataset of the human developing lung. 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.”

Implications for the future

“The Developmental Lung Cell Atlas” is part of the Human Cell Atlas initiative which aims to map every cell type in the human body. Dr Sarah Teichmann, co-senior author from the Wellcome Sanger Institute and Co-Founder of the Human Cell Atlas, said: “A complete Human Cell Atlas, detailing all stages of life, will help explain many aspects of human health and disease. This includes the cells that are the building blocks of organs as they form in early life, which we lose as an adult. Our Developmental Lung Cell Atlas allows us to look at the stages and pathways that adult lung cells have gone through, and how these early phases influence disease later on. This is an important contribution towards the first draft of the Human Cell Atlas.”

The findings of this study not only provide new insights into the early stages of lung development but The Developmental Lung Cell Atlas, which is available online, has interactive datasets, with comprehensive and detailed information, allowing researchers to investigate the origins of lung diseases, create models to study lung conditions, and test out potential therapies.

As well as providing new insights into the early stages of lung development, the authors have also made The Developmental Lung Cell Atlas available online. This resource includes interactive datasets, with comprehensive and detailed information, allowing researchers to investigate the origins of lung diseases, create models to study lung conditions and test out potential therapies.