Consensus Lung Cell Reference: The Collaborative Cross-Consortium and Country Lung Cell Nomenclature Project (C3LCN). An Official American Thoracic Society Workshop Report.

Abstract

Rapid advances in single-cell technologies now allow measurement of thousands of transcripts and other molecular features of individual cells offering unprecedented insight into lung biology in homeostasis and in disease. The accelerated generation of multimodal data has, however, been accompanied by the reporting of putatively "novel" cell types described without consensus regarding their ontogeny, identity, function, or defining markers. To fully realize the value of the technological advances and to enable rigorous comparison across studies, respiratory research will benefit from standardized, quantitative, and biologically grounded cell classifications and nomenclature. Achieving the transformative potential of the multimodal data will depend on common, machine- and human-readable nomenclature, structured and expandable dictionary and atlas resources, and clear methodological standards that ensure consistency as technologies evolve. The American Thoracic Society (ATS) recognized the importance of promoting a common nomenclature to enhance equitable access and utility of the vast amounts of multimodal data generated by the lung research community. The Collaborative Cross-Consortium and Country Lung Cell Nomenclature Project (C3LCN) was adopted as an ATS Assembly Project in 2024. This is the consensus report outlining the goals and framework of the Project to foster coordinated progressive lung cell research to include: 1) providing best practices for analysis, publication and reporting of lung single-cell transcriptomic datasets; 2) establishing a contemporary lexicon for healthy adult human cells of the lower respiratory tract with structured, persistent, and resolvable identifiers; 3) defining a scalable taxonomy to organize a common lung cell nomenclature; 4) offering tools to support collaboration, knowledge dissemination, and translational advances rooted in modern lung biology augmenting, not replacing, pre-genomic biological knowledge; and 5) describing an infrastructure capable of incorporating new ontological refinements as higher-resolution, multimodal single-cell and spatial datasets emerge, cellular heterogeneity is better defined, and disease-associated abnormal cell types and reactive cell states are increasingly recognized and mechanistically interrogated. Together, this coordinated effort aims to provide the foundation necessary for a robust, harmonized, and expandable nomenclature for lung science.