Journal article
Cellular and molecular architecture of submucosal glands in wild-type and cystic fibrosis pigs
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.119(4), e2119759119
2022
DOI: 10.1073/pnas.2119759119
PMCID: PMC8794846
PMID: 35046051
Abstract
Submucosal glands (SMGs) protect lungs but can also contribute to disease. For example, in cystic fibrosis (CF), SMGs produce abnormal mucus that disrupts mucociliary transport. CF is an ion transport disease, yet knowledge of the ion transporters expressed by SMG acini, which produce mucus, and SMG ducts that carry it to the airway lumen is limited. Therefore, we isolated SMGs from newborn pigs and used single-cell messenger RNA sequencing, immunohistochemistry, and in situ hybridization to identify cell types, gene expression, and spatial distribution. Cell types and transcript levels were the same in non-CF and CF SMGs, suggesting that loss of epithelial anion secretion rather than an intrinsic cell defect causes CF mucus abnormalities. Gene signatures of acinar mucous and acinar serous cells revealed specialized functions in producing mucins and antimicrobials, respectively. However, surprisingly, these two cell types expressed the same ion transporters and neurohumoral receptors, suggesting the importance of balancing mucin and liquid secretion to produce optimal mucus properties. SMG duct cell transcripts suggest that they secrete HCO3- and Cl-, and thus have some similarity to pancreatic ducts that are also defective in CF. These and additional findings suggest the functions of the SMG acinus and duct and provide a baseline for understanding how environmental and genetic challenges impact their contribution to lung disease.
Details
- Title: Subtitle
- Cellular and molecular architecture of submucosal glands in wild-type and cystic fibrosis pigs
- Creators
- Wenjie Yu - University of IowaThomas O Moninger - University of IowaAndrew L Thurman - University of IowaYuliang Xie - University of IowaA Jain - University of IowaK Zarei - University of IowaLinda S Powers - University of IowaAlejandro A Pezzulo - University of IowaDavid A Stoltz - University of IowaMichael J Welsh - University of Iowa
- Resource Type
- Journal article
- Publication Details
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.119(4), e2119759119
- DOI
- 10.1073/pnas.2119759119
- PMID
- 35046051
- PMCID
- PMC8794846
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 1091-6490
- Grant note
- DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: HL091842; DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: HL091842; DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: HL051670; DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: HL051670; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation, award: RDP; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation, award: RDP
- Language
- English
- Date published
- 2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984239418702771
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