Need Help?

Single cell RNA-seq mapping of nasal and tracheobronchial airways in human healthy volunteers

The respiratory tract constitutes an elaborated line of defense based on a unique cellular ecosystem. Single-cell profiling methods enable the investigation of cell population distributions and transcriptional changes along the airways. We have explored cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. 77,969 cells were collected by bronchoscopy at 35 distinct locations, from the nose to the 12th division of the airway tree. The resulting atlas is composed of a high percentage of epithelial cells (89.1%), but also immune (6.2%) and stromal (4.7%) cells with peculiar cellular proportions in different sites of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type specific gene expression was stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuro-endocrine (PNEC) and brush cells, which are likely derived from a common population of precursor cells. We also report a population of KRT13 positive cells with a high percentage of dividing cells which are reminiscent of “hillock” cells previously described in mouse. Robust characterization of this unprecedented large single-cell cohort establishes an important resource for future investigations. The precise description of the continuum existing from nasal epithelium to successive divisions of lung airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001005714 NextSeq 500 35
Publications Citations
A practical solution to pseudoreplication bias in single-cell studies.
Nat Commun 12: 2021 738
Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19.
J Clin Invest 131: 2021 148517
Human distal lung maps and lineage hierarchies reveal a bipotent progenitor.
Nature 604: 2022 111-119
Altered host protease determinants for SARS-CoV-2 Omicron.
Sci Adv 9: 2023 eadd3867
Transcriptomic profiles of age-related genes in female trachea and bronchus.
Front Genet 14: 2023 1120350
Convergence of YAP/TAZ, TEAD and TP63 activity is associated with bronchial premalignant severity and progression.
J Exp Clin Cancer Res 42: 2023 116
An integrated cell atlas of the lung in health and disease.
Nat Med 29: 2023 1563-1577
Guided construction of single cell reference for human and mouse lung.
Nat Commun 14: 2023 4566
SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters<sup>1</sup>.
Emerg Microbes Infect 12: 2023 2245921
Cancer-prone Phenotypes and Gene Expression Heterogeneity at Single-cell Resolution in Cigarette-smoking Lungs.
Cancer Res Commun 3: 2023 2280-2291