"The lung is a very complex organ and only now, by using new technologies, multiple cell types have been identified," said one of the study's authors Mauricio Rojas, MD, professor and associate vice chair of research in internal medicine at The Ohio State University Wexner Medical Center and College of Medicine. "This manuscript is the result of a worldwide collaborative effort in which investigators in the United States, Europe and Australia have shared their data, resulting in a large database, that has allowed us to identify more than 50 different cell types of the lung. These will help us to understand progress like aging, and diseases like COPD and lung fibrosis."
By combining data from nearly 40 studies, researchers created the first integrated single-cell atlas of the lung, revealing rare cell types and highlighting cellular differences between healthy people. In addition, the study found common cell states between lung fibrosis, cancer and COVID-19, offering new ways of understanding lung disease, which could help identify new therapeutic targets.
This study is part of the global Human Cell Atlas initiative to map every cell type in the human body, to transform the understanding of health, infection and disease. Lung research has benefited greatly from recent single-cell studies that show which genes are active in each cell. Despite this, the research has been limited by the number of samples and individuals included per study. To better understand healthy lungs and determine what goes wrong in disease, a comprehensive atlas has been needed, however this has been difficult to achieve.
Now, a large team of researchers has successfully combined 49 lung datasets into a single integrated Atlas, using advanced machine learning. By pooling and integrating datasets from every major single-cell RNA-sequencing lung study published to date, the team created the first integrated Human Lung Cell Atlas. This Atlas spans over 2.4 million cells from 486 individuals and gives new insights into lung biology that were not possible before.
While the core of the Human Lung Cell Atlas is data from healthy lungs, the team also took datasets from more than 10 different lung diseases and projected these onto the healthy data, to understand disease states. The team discovered that different lung diseases shared common immune cell states, including the finding that a subset of macrophages (a type of immune cell) shared similar gene activity in lung fibrosis, cancer and COVID-19. The shared states indicate that these cells could play a similar role in scar formation in the lung in all three diseases and provide pointers for potential therapeutic targets.
The Lung Atlas Integration project was an international collaborative effort with nearly 100 partners from more than 60 departments. The team are part of the Human Cell Atlas Lung Biological Network, which has its roots in the Chan Zuckerberg Initiative Seed Networks for the Human Cell Atlas, and the European Union funded lung network DiscovAIR. At the start of the COVID-19 pandemic in 2020, the single-cell lung communities came together rapidly, forming the HCA Lung Biological Network to help understand COVID-19, which then led to the global effort to integrate all the data.
The first integrated major organ within the Human Cell Atlas initiative, the Human Lung Cell Atlas is publicly available for researchers globally, as a central resource to study the lung in health and disease.
