Journal article
Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition
Nature medicine, Vol.27(5), pp.806-814
05/2021
DOI: 10.1038/s41591-021-01332-7
PMCID: PMC9009537
PMID: 33958799
Abstract
Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts more than 70,000 people. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most important determinant of morbidity and mortality. Here we report results from a multi-institute consortium in which single-cell transcriptomics were applied to define disease-related changes by comparing the proximal airway of CF donors (n = 19) undergoing transplantation for end-stage lung disease with that of previously healthy lung donors (n = 19). Disease-dependent differences observed include an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subsets coupled with an unexpected decrease in cycling basal cells. Our study yields a molecular atlas of the proximal airway epithelium that will provide insights for the development of new targeted therapies for CF airway disease.
Details
- Title: Subtitle
- Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition
- Creators
- Gianni Carraro - Cedars-Sinai Medical CenterJustin Langerman - University of California, Los AngelesShan Sabri - University of California, Los AngelesZareeb Lorenzana - Hastings CenterArunima Purkayastha - Mattel Children's HospitalGuangzhu Zhang - Cedars-Sinai Medical CenterBindu Konda - Cedars-Sinai Medical CenterCody J Aros - University of California, Los AngelesBen A Calvert - Hastings CenterAleks Szymaniak - Cystic Fibrosis FoundationEmily Wilson - Cystic Fibrosis FoundationMichael Mulligan - Cystic Fibrosis FoundationPriyanka Bhatt - Cystic Fibrosis FoundationJunjie Lu - Cystic Fibrosis FoundationPreethi Vijayaraj - Mattel Children's HospitalChangfu Yao - Cedars-Sinai Medical CenterDavid W Shia - University of California, Los AngelesAndrew J Lund - Mattel Children's HospitalEdo Israely - Cedars-Sinai Medical CenterTammy M Rickabaugh - Mattel Children's HospitalJason Ernst - University of California, Los AngelesMartin Mense - Cystic Fibrosis FoundationScott H Randell - University of North Carolina at Chapel HillEszter K Vladar - University of Colorado DenverAmy L Ryan - Hastings CenterKathrin Plath - University of California, Los AngelesJohn E Mahoney - Cystic Fibrosis FoundationBarry R Stripp - Cedars-Sinai Medical CenterBrigitte N Gomperts - Mattel Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.27(5), pp.806-814
- DOI
- 10.1038/s41591-021-01332-7
- PMID
- 33958799
- PMCID
- PMC9009537
- NLM abbreviation
- Nat Med
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Grant note
- F31 CA239655 / NCI NIH HHS Howard Hughes Medical Institute T32 CA009056 / NCI NIH HHS U66 IP000597 / NCIRD CDC HHS DP1 DA044371 / NIDA NIH HHS R01 CA208303 / NCI NIH HHS P01 HL108793 / NHLBI NIH HHS KL2 TR001882 / NCATS NIH HHS T32 GM008042 / NIGMS NIH HHS P01 GM099134 / NIGMS NIH HHS P30 DK065988 / NIDDK NIH HHS
- Language
- English
- Date published
- 05/2021
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984284450602771
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