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  11. Human Airway Submucosal Gland Organoids To Study Respiratory Inflammation And Infection

Human airway submucosal gland organoids to study respiratory inflammation and infection

Lin Lin1, Carla Pou Casellas2, Antonella F M Dost3

  • 1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center, Utrecht 3584 CT, the Netherlands; Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Oncode Institute, Hubrecht Institute, Utrecht 3584 CT, the Netherlands; Princess Maxima Center for Pediatric Oncology, Utrecht 3584 CS, the Netherlands.

Cell Stem Cell
|June 13, 2025

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View abstract on PubMed

Summary
This summary is machine-generated.

Submucosal glands (SMGs) in the airway lining are crucial but understudied in respiratory models. This research developed distinct SMG organoids, revealing their unique cell types and susceptibility to viral infection, enhancing airway disease modeling.

Keywords:
ANPEPCD13MUC5Bairway inflammation

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Area of Science:

  • Respiratory biology
  • Cellular and molecular physiology
  • In vitro modeling

Background:

  • The human airway lining comprises surface airway epithelium (SAE) and submucosal glands (SMGs).
  • SMGs are critical for airway function but are underrepresented in current in vitro models of respiratory diseases.
  • Understanding SMG physiology is essential for accurate modeling of airway inflammation and infection.

Purpose of the Study:

  • To develop and characterize distinct organoid models for SAE and SMGs.
  • To investigate the unique cellular composition and physiological responses of SMGs.
  • To assess the utility of these organoids in modeling respiratory viral infections.

Main Methods:

  • Long-term culture of organoids derived separately from human SAE and SMGs.
  • Single-cell RNA sequencing (scRNA-seq) to analyze cellular heterogeneity.
  • Cytokine exposure and infection assays using human alpha-coronavirus 229E (HCoV-229E).

Main Results:

  • Organoid models accurately recapitulated the cellular heterogeneity of native SAE and SMGs.
  • SMG organoids showed enrichment in MUC5B-producing mucous cells and alpha-smooth muscle actin (αSMA)-expressing myoepithelial cells.
  • CD13-positive SMG secretory cells demonstrated selective vulnerability to HCoV-229E infection, initiating an unfolded protein response.

Conclusions:

  • Distinct SAE and SMG organoid models provide faithful representations of airway tissue compartments.
  • SMG organoids are valuable tools for studying specific cellular responses to inflammatory stimuli and viral pathogens.
  • These findings expand the application of airway organoids for respiratory (patho)physiology research.
airway submucosal gland
coronavirus infection
human airway organoids
mucous cells