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A single-cell atlas of the human healthy airways

Marie Deprez, View ORCID ProfileLaure-Emmanuelle Zaragosi, Marin Truchi, Sandra Ruiz Garcia, Marie-Jeanne Arguel, Kevin Lebrigand, Agnès Paquet, Dana Pee’r, Charles-Hugo Marquette, Sylvie Leroy, View ORCID ProfilePascal Barbry
doi: https://doi.org/10.1101/2019.12.21.884759
Marie Deprez
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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Laure-Emmanuelle Zaragosi
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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  • ORCID record for Laure-Emmanuelle Zaragosi
Marin Truchi
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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Sandra Ruiz Garcia
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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Marie-Jeanne Arguel
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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Kevin Lebrigand
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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Agnès Paquet
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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Dana Pee’r
3Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
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Charles-Hugo Marquette
2Université Côte d’Azur, CHU de Nice, FHU OncoAge, CNRS, Inserm, IRCAN team 3, Pulmonology Department, Nice, 06000, France
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Sylvie Leroy
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
2Université Côte d’Azur, CHU de Nice, FHU OncoAge, CNRS, Inserm, IRCAN team 3, Pulmonology Department, Nice, 06000, France
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Pascal Barbry
1Université Côte d’Azur, CNRS, IPMC, Sophia-Antipolis, 06560, France
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  • ORCID record for Pascal Barbry
  • For correspondence: barbry@ipmc.cnrs.fr
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Abstract

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 12th 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.

Footnotes

  • https://www.genomique.eu/cellbrowser/HCA/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 23, 2019.
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A single-cell atlas of the human healthy airways
Marie Deprez, Laure-Emmanuelle Zaragosi, Marin Truchi, Sandra Ruiz Garcia, Marie-Jeanne Arguel, Kevin Lebrigand, Agnès Paquet, Dana Pee’r, Charles-Hugo Marquette, Sylvie Leroy, Pascal Barbry
bioRxiv 2019.12.21.884759; doi: https://doi.org/10.1101/2019.12.21.884759
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A single-cell atlas of the human healthy airways
Marie Deprez, Laure-Emmanuelle Zaragosi, Marin Truchi, Sandra Ruiz Garcia, Marie-Jeanne Arguel, Kevin Lebrigand, Agnès Paquet, Dana Pee’r, Charles-Hugo Marquette, Sylvie Leroy, Pascal Barbry
bioRxiv 2019.12.21.884759; doi: https://doi.org/10.1101/2019.12.21.884759

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