Abstract
The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here we present the first comprehensive single cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiple in vitro models of benign and malignant mesothelial cells, and characterise these through comparison with in vivo transcriptomic data. While bulk pleural transcriptomes have been reported previously, this is the first study to provide resolution at single cell level. We expect our pleural cell atlas will prove invaluable to those studying pleural biology and disease. For example, it has already enabled us to shed light on the transdifferentiation of mesothelial cells allowing us to develop a simple method for prolonging mesothelial cell differentiation in vitro.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflicts of interest: In addition to the funding acknowledged above, the following conflicts are declared by the authors.
Conflicts of interest: JO reports grants from Victor Dahdaleh Charitable Foundation.
Conflicts of interest: RN none. TSA none. JCS none. JAV none. NV none. ALW none. JF none. JH none. GA none.
Conflicts of interest: ASC reports grants for Innovate UK, consultancy for Viderigen, honoraria for lecture for Astra Zeneca, book royalties from Springer Nature, payment for expert testimony for Medicolegal reports, leadership or fiduciary roles for Society for Cardiothoracic Surgery of GB & Ireland, and Chair of thoracic surgery committeeNHS, National Clinical lead for NHS England, Governor of Royal Papworth Hospital.
Conflicts of interest: AP reports lecture honoraria from AstraZeneca, travel support from Albyn Medical.
Conflicts of interest: GB none.
Conflicts of interest: NK is a scientific founder at Thyron, served as a consultant to Biogen Idec, Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Theravance, LifeMax, Three Lake Partners, Optikira, Astra Zeneca, RohBar, Veracyte, Augmanity, CSL Behring, Galapagos, Gilead, Chiesi, Arrowhead, Sofinnova and Thyron over the last 3 years, reports Equity in Pliant and Thyron, and grants from Veracyte, Boehringer Ingelheim, BMS, Three Lakes Foundation, and non-financial support from MiRagen and Astra Zeneca. NK also has the following patents licenced to biotech: New therapies for IPF, New Therapies for ARDS, New Biomarkers in IPF.
Conflicts of interest: HF none. DMR none.
Conflicts of interest: MG reports consultancy fees from and equity in Mosaic Therapeutics, and has a patent pending for describing suspension organoid cultures.
Conflicts of interest: RCR is Chief Investigator of Mesobank UK and is part funded by Asthma and Lung UK.
Conflicts of interest: SJM none.
This is a PDF-only article. Please click on the PDF link above to read it.
- Received January 26, 2023.
- Accepted October 30, 2023.
- Copyright ©The authors 2024.
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
