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A single-cell atlas of the human healthy airways
Open accessAbstract
Rationale: 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. Methods: 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 12 th division of the airway tree. Results: 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. Conclusions: 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.
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Analyzed samples in prior human upper airway scSeq datasets did not include any olfactory sensory neurons or sustentacular cells, indicating that tissue sampling did not include the olfactory epithelium.
“However, analyzed samples in these datasets did not include any OSNs or sustentacular cells, indicating that tissue sampling in these experiments did not include the OE (41, 42).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [41]
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Metadata
- Authors
- Deprez, M., Zaragosi, L.-E., Truchi, M., Garcia, S. R., Arguel, M.-J., Lebrigand, K., Paquet, A., Pee’r, D., Marquette, C.-H., Leroy, S., & Barbry, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Barbry, Pascal
- ORCID
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- openRxiv
- Published
- 2019-12-23
- Volume
- 202
- Issue
- 12
- Pages
- 1636-1645
- ISSN
- 1073-449X (ISSN-L)
- OpenAlex
- W3045953207
- Cited by
- 493
- References
- 47
- Citations by year
- 2026: 56 · 2025: 89 · 2024: 83 · 2023: 95 · 2022: 78 · 2021: 62 · 2020: 29 · 2019: 1
- FWCI
- 21.41
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR-19-P3IA-0002, ANR-10-INBS-0009, ANR-15-IDEX-0001, ANR-19-CE14-0027)
- Agence Nationale de Sécurité du Médicament et des Produits de Santé
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Keywords
- human airway epithelium, single-cell atlas, gene expression profiling, suprabasal cells, secretory cells, multiciliated cells, ionocytes, pulmonary neuroendocrine cells, brush cells, keratin 13, squamous cells, tracheobronchial airways, nasal epithelium, MUC4, SCGB1A1, TFF3
- MeSH terms
- Adult, Aged, Aged, 80 and over, Bronchi, Cell Differentiation, Epithelial Cells, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Nasal Mucosa, Stromal Cells, Cell Proliferation, Healthy Volunteers
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