A comprehensive lung cell atlas provides insight into unexpected immune niches in the airway

The Wellcome Sanger Institute and collaborators’ most comprehensive lung cell atlas to date reveals 11 novel lung cell types and provides detailed insight into the immune processes involved in fighting lung infections.

Published today (December 21, 2022) natural geneticsthis freely available resource focuses on the multiple immune cells, barrier cells, and their environment within the lung that are implicated in respiratory diseases and infections.

This new lung cell atlas, part of the broader international Human Cell Atlas initiative, combines single-cell sequencing and spatial transcriptomics to explore how cells interact and communicate with each other. provides a complete picture of what

Single-cell studies have advanced our understanding of lung function, but the lung consists of a complex structure and environment that cannot be investigated by single-cell sequencing alone. For example, there are many open questions about how cells are organized and how specific cell types, especially rare cell types, contribute to lung disease.

Chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease are leading causes of death worldwide.¹Understanding the communication between cells within the local environment of healthy lungs can help us determine what is being destroyed in disease and give clues as to how this can be prevented or treated.

In this study, Wellcome Sanger Institute researchers and collaborators genetically profiled approximately 200,000 cells from lung tissue from 13 donors, discovered 11 new cell types, and transformed a total of 80 cell types. indicated the exact location.

Among these new cell types, peribronchial fibroblasts have been found to be involved in COPD and idiopathic pulmonary fibrosis. Further studies are needed to investigate how these cells are involved, but this finding may reveal new links between cellular pathways and disease using this lung atlas. is shown.

The ability to analyze multiple locations in the same lung provided important information about different cells in a single study. Many of which were previously unmapped. Moreover, the associations discovered between peribronchial fibroblasts and chronic lung disease demonstrate that this atlas can go beyond reference data and provide new insights into disease. “

Dr. Elo Madissoon, co-first author and postdoctoral fellow at the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute (EMBL-EBI)

In addition to this, the researchers were able to define a lung microenvironment called the gland-associated immune niche (GAIN). GAIN exists to help fight respiratory infections, ultimately boosting her IgA antibody production. This is the first study to successfully map this complex process in detail.

IgA responses are critical for efficient protection against respiratory infections and are impaired in lung diseases such as COPD and cystic fibrosis. Further studies investigating GAIN function may help develop therapies to alleviate disease symptoms, improve resistance to infection, or create ways to enhance vaccine response.

Dr. Amanda Oliver, co-first author and postdoctoral fellow at the Wellcome Sanger Institute, said: Epithelial, endothelial, and immune cells interact to form an immune niche -; GAIN -; which may be important for protection against respiratory infections. Our single-cell data allows us to delve into the signaling circuits that enable this immune niche to function, which may be important in developing new ways to treat disease in the future. “

Dr. Kirsten Meyer, co-senior author and principal scientist at the Wellcome Sanger Institute, said: Our study is based on the single-cell era and by including spatial data we are beginning to understand how lung cells interact in specific microenvironments. Understanding how they interact is important if we want to pinpoint where something is.Our atlas is a valuable resource for the scientific community, showing how the lungs function at the cellular level. We look forward to large-scale studies that piece together the complete puzzle of what to do.”

Co-senior author Sarah Teichmann, Ph.D., director of cytogenetics at the Wellcome Sanger Institute and co-founder of the Human Cell Atlas, said: Our lung cell atlas gives greater insight into vital organ function and is an important contribution towards a complete human cell atlas. It helps us identify which pathway or cell in the organ is which pathway or cell. We would like to thank the organ donors and their families and loved ones for making this study possible.”