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Role of stromal cells during human iPSC differentiation into bronchial epithelium

Amel Nasri, Florent Foisset, Engi Ahmed, Isabelle Vachier, Said Assou, Arnaud Bourdin, John De Vos
European Respiratory Journal 2021 58: PA3686; DOI: 10.1183/13993003.congress-2021.PA3686
Amel Nasri
1IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France
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  • For correspondence: amel.nasri@inserm.fr
Florent Foisset
1IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France
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Engi Ahmed
2Department of Respiratory Diseases, CHU Montpellier, PhyMedExp Inserm U1046 CNRS, Montpellier, France
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Isabelle Vachier
2Department of Respiratory Diseases, CHU Montpellier, PhyMedExp Inserm U1046 CNRS, Montpellier, France
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Said Assou
1IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France
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Arnaud Bourdin
2Department of Respiratory Diseases, CHU Montpellier, PhyMedExp Inserm U1046 CNRS, Montpellier, France
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John De Vos
1IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France
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Abstract

Background: Chronic airway diseases are a common medical condition worldwide including diseases such as cystic fibrosis, asthma or COPD. Induced pluripotent stem cells (iPSC) provide a new approach to study lung diseases. We and others have recently generated functional airway multiciliated epithelium in air-liquid interface culture conditions from human iPSC (iALI) (Ahmed et al., BioRxiv, 2020). During this differentiation process, a mesenchymal stromal component is consistently described but poorly studied.

Objective/Methods: To comprehensively define the cell types, mechanisms, and mediators driving iALI model, we performed single-cell mRNA sequencing. RT-qPCR and immunofluorescence assays were used to confirm the sequencing results.

Results: In addition to the epithelial cell subtypes, the iALI cultures also contain a previously poorly documented EPCAM-COL1A1+DCN+ mesenchymal stromal compartment. Several populations, that partially overlap can be identified: 1/ACTA2+ myofibroblasts including fibromyocytes characterized by high expression of contractile genes such as CNN1 and TAGLN, 2/ a transition population closer to epithelial cells expressing MAF and the long non coding mRNA EPB41L4A-AS1 and 3/ a highly proliferating PCNA+CDK1+ cells. Moreover, stromal cells expressed growth factors such as FGF10 while its receptor FGFR2 is expressed on the epithelial cells, suggesting that stromal cells could support iALI development.

Conclusion: These data provide high-resolution insights into the complexity and plasticity of the iALI suggesting that a crosstalk between epithelium and mesenchyme can contribute to iALI development. The functional role of the relevant pathways will be assessed in our iALI model.

  • Lung growth/development
  • Epithelial cell
  • COPD - mechanism

Footnotes

Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3686.

This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2021
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Role of stromal cells during human iPSC differentiation into bronchial epithelium
Amel Nasri, Florent Foisset, Engi Ahmed, Isabelle Vachier, Said Assou, Arnaud Bourdin, John De Vos
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3686; DOI: 10.1183/13993003.congress-2021.PA3686

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Role of stromal cells during human iPSC differentiation into bronchial epithelium
Amel Nasri, Florent Foisset, Engi Ahmed, Isabelle Vachier, Said Assou, Arnaud Bourdin, John De Vos
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3686; DOI: 10.1183/13993003.congress-2021.PA3686
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