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Single-Cell Lung Atlases Reveal New Cell Types, Asthma-Related Alterations

NEW YORK (GenomeWeb) – Insights gleaned from gene expression profiling on thousands of single lung cells from individuals with or without asthma have identified interactions between new and known cell types along the respiratory route, including those that become altered in asthma.

Researchers from the Wellcome Sanger Institute, University Medical Center Groningen, the Open Targets partnership, and elsewhere relied on single-cell transcriptomics to assess more than 36,000 individual lung cells from 17 individuals. Their findings, published online today in Nature Medicine, uncovered previously unappreciated memory T cell types in the lung, for example, as well as pathogenic effector type 2 helper T cells and mucous ciliated epithelial cells found in lung samples from individuals with asthma.

"Our large-scale, open access data reveals the activity of different cells, their communication pathways and locations," co-senior author Sarah Teichmann, a cellular genetics researcher affiliated with the Sanger Institute, University of Cambridge, and Open Targets, said in a statement, explaining that the cell atlas "will provide a great resource for further lung research and we hope that it will enable the identification of potential new therapeutic targets for asthma relief."

For the Human Cell Atlas initiative, she and her colleagues did 10x Genomics Chromium droplet single-cell RNA-seq analyses on 36,931 individual cells isolated from sites along the airway. These included cells collected from the upper and lower airway and into lung's parenchyma sites, where gas exchange occurs.

"We describe the cellular landscape of human lung tissue at the single-cell level, charting differences in frequencies and molecular state of lung structural and inflammatory cells between upper and lower airways and parenchyma," the authors explained.

In the healthy lung participants, for example, the team saw CD4+ circulating memory T cells and tissue-resident memory T cells that had not been characterized in the lung in the past. It also spelled out 10 epithelial cell types — determined from gene expression clusters — and their relationships with one another at sites along the airway.

"Our single-cell analysis identifies differences in the proportions and transcriptional phenotype of structural and inflammatory cells between upper and lower airways and lung parenchyma," the authors reported, noting that "many disease-associated genes have highly cell type-specific expression patterns."

When it came to samples from individuals with asthma, meanwhile, the investigators described new mucous ciliated cells and goblet cells that seemed to contribute to hyperplasia in the lower airway. They also uncovered intraepithelial mast cells, pathogenic effector type 2 helper T cells, and type 2 cytokine immune cells in those with asthma, along with broader shifts in the cell-cell interactions and diminished structural cell communication in the lung.

Typically, "all kinds of cells communicate with each other in order to keep the airways functioning well," co-senior author Martijn Nawijn, a pathology and medical biology researcher at the University Medical Center Groningen, said in a statement.

"But in asthma patients, almost all of those interactions are lost," he explained. "Instead of a network of interactions, in asthma the inflammatory cells seem to completely dominate the communication in the airways."

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