Journal article
A Single-Cell Atlas of Large and Small Airways at Birth in a Porcine Model of Cystic Fibrosis
American journal of respiratory cell and molecular biology, Vol.66(6), pp.612-622
03/02/2022
DOI: 10.1165/rcmb.2021-0499OC
PMCID: PMC9163647
PMID: 35235762
Abstract
Lack of CFTR affects the transcriptome, composition, and function of large and small airway epithelia in people with advanced cystic fibrosis (CF); however, whether lack of CFTR causes cell-intrinsic abnormalities present at birth vs. inflammation-dependent abnormalities is unclear. We performed a single cell RNA-seq census of micro-dissected small airways from newborn CF pigs, which recapitulate CF host defense defects and pathology over time. Lack of CFTR minimally affected the transcriptome of large and small airways at birth, suggesting that infection and inflammation drive transcriptomic abnormalities in advanced CF. Importantly, common small airway epithelial cell types expressed a markedly different transcriptome than corresponding large airway cell types. Quantitative immunohistochemistry and electrophysiology of small airway epithelia demonstrated basal cells that reach the apical surface and a water and ion transport advantage. This single cell atlas highlights the archetypal nature of airway epithelial cells with location-dependent gene expression and function.
Details
- Title: Subtitle
- A Single-Cell Atlas of Large and Small Airways at Birth in a Porcine Model of Cystic Fibrosis
- Creators
- Andrew L Thurman - University of IowaXiaopeng Li - Michigan State UniversityRaul Villacreses - University of IowaWenjie Yu - University of IowaHuiyu Gong - University of IowaSteven E Mather - University of IowaGuillermo S Romano-Ibarra - University of IowaDavid K Meyerholz - University of IowaDavid A Stoltz - University of IowaMichael J Welsh - University of IowaIan M Thornell - University of IowaJoseph Zabner - University of IowaAlejandro A Pezzulo - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.66(6), pp.612-622
- DOI
- 10.1165/rcmb.2021-0499OC
- PMID
- 35235762
- PMCID
- PMC9163647
- NLM abbreviation
- Am J Respir Cell Mol Biol
- eISSN
- 1535-4989
- Grant note
- DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: P30DK054759; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation, award: Iowa RDP, LI19XX0, PEZZUL20A1-KB; DOI: 10.13039/100005564, name: Gilead Sciences, award: Gilead Sciences Research Scholars Program in Cysti; DOI: 10.13039/100000050, name: National Heart, Lung, and Blood Institute, award: K01HL140261, P01HL051670, P01HL091842, T32GM007337, T32HL007638
- Language
- English
- Date published
- 03/02/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pathology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984227002902771
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