Lungmap 2.0 maps the epigenome of diverse cells of the human lung

The human lungs comprise an intricate network of epithelial, mesenchymal, endothelial, and hematopoietic cells. These diverse cell types come together to form the cellular niches that collectively regulate lung function in health and disease. Although this cellular census has been characterized by large-scale transcriptomic approaches like RNA-seq, no studies have looked deeper to resolve the cis-regulatory elements (CREs) that ultimately control cell type-specific responses throughout the lifespan of the human lung during health and disease.

Dr. Xin Sun, Professor of Pediatrics at University of California San Diego, teamed up with the Center to map this uncharted frontier using single-nuclei ATAC-seq (snATAC-seq) as part of Phase 2 of the Molecular Atlas of Lung Development Program (LungMAP, www.LungMAP.net).

The snATAC-seq dataset generated by Sun and the Center provides an epigenomic atlas of every major cell type in the human lung — even the rare pulmonary neuroendocrine cells that make up less than 1% of the lung’s cellular constituency. Sun believes the dataset will provide a valuable resource for those interested in probing the epigenome of the nondiseased lung across the human lifespan.

The dataset has already bore fruit: Sun and the Center discovered candidate CREs associated with a SARS-CoV-2 viral entry receptor that become more active with age in alveolar type 2 cells. The insight offers a clue into why children are less susceptible to COVID-19.

The dataset was published by eLife in November 2020. Center Associate Directors Drs. Allen Wang and Sebastian Pressl were co-authors on the paper. The snATAC-seq dataset is one of over 700 generated by the Center’s Single- Cell Epigenomics Platform.

A nationwide consortium, the LungMAP 2 team consists of five research centers (UC San Diego, University of Rochester, University of Pennsylvania, Pacific Northwest National Laboratory, and Cincinnati Children’s Hospital) and a multi-institution data coordination center (Cincinnati Children’s Hospital, Broad Institute of MIT and Harvard, University of California Santa Cruz). Its overarching goal is to generate detailed, single-cell maps of the human lung across development. Using a combination of high-resolution multi-omic and imaging technologies, the consortium aims to understand the relationship between the lung’s molecular makeup, spatial organization, and function. The goal is to leverage this knowledge to understand and eventually develop treatments for lung diseases like bronchopulmonary dysplasia, congenital diaphragmatic hernia, childhood interstitial lung disease, and pulmonary hypertension.