Journal article
Human distal airways contain a multipotent secretory cell that can regenerate alveoli
Nature (London), Vol.604(7904), pp.120-126
04/2022
DOI: 10.1038/s41586-022-04552-0
PMCID: PMC9297319
PMID: 35355013
Abstract
The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.
Details
- Title: Subtitle
- Human distal airways contain a multipotent secretory cell that can regenerate alveoli
- Creators
- Maria C Basil - University of PennsylvaniaFabian L Cardenas-Diaz - University of PennsylvaniaJaymin J Kathiriya - University of California, San FranciscoMichael P Morley - University of PennsylvaniaJustine Carl - University of PennsylvaniaAlexis N Brumwell - University of California, San FranciscoJeremy Katzen - University of PennsylvaniaKatherine J Slovik - University of PennsylvaniaApoorva Babu - University of PennsylvaniaSu Zhou - University of PennsylvaniaMadison M Kremp - University of PennsylvaniaKatherine B McCauley - Boston UniversityShanru Li - University of PennsylvaniaJoseph D Planer - University of PennsylvaniaShah S Hussain - University of Alabama at BirminghamXiaoming Liu - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USARebecca Windmueller - University of PennsylvaniaYun Ying - University of PennsylvaniaKathleen M Stewart - University of PennsylvaniaMichelle Oyster - University of PennsylvaniaJason D Christie - University of PennsylvaniaJoshua M Diamond - University of PennsylvaniaJohn F Engelhardt - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USAEdward Cantu - University of PennsylvaniaSteven M Rowe - University of Alabama at BirminghamDarrell N Kotton - Boston UniversityHarold A Chapman - University of California, San FranciscoEdward E Morrisey - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.604(7904), pp.120-126
- DOI
- 10.1038/s41586-022-04552-0
- PMID
- 35355013
- PMCID
- PMC9297319
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- R01 HL087825 / NHLBI NIH HHS U01 HL134766 / NHLBI NIH HHS P30 DK072482 / NIDDK NIH HHS U01 HL152978 / NHLBI NIH HHS R35 HL150767 / NHLBI NIH HHS HL134745 / NIH HHS HL148857 / NIH HHS K23 HL121406 / NHLBI NIH HHS R01 HL132999 / NHLBI NIH HHS K08 HL130586 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284324602771
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