Human distal airways contain a multipotent secretory cell that can regenerate alveoli.

Animals Bronchioles / cytology Cell Lineage Ferrets Humans Lung / pathology Mice Multipotent Stem Cells / cytology Pulmonary Alveoli / cytology Pulmonary Disease, Chronic Obstructive

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
04 2022
Historique:
received: 03 02 2021
accepted: 14 02 2022
pubmed: 1 4 2022
medline: 19 4 2022
entrez: 31 3 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41586-022-04552-0 PMID: 35355013 PMC: PMC9297319
pubmed: 35355013
doi: 10.1038/s41586-022-04552-0
pii: 10.1038/s41586-022-04552-0
pmc: PMC9297319
mid: NIHMS1802781
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

120-126

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK072482
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL150226
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007586
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL163398
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135816
Pays : United States
Organisme : NIH HHS
ID : HL148857
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL148857
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NIH HHS
ID : HL134745
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL150767
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL130586
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL152978
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Maria C Basil (MC)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Fabian L Cardenas-Diaz (FL)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jaymin J Kathiriya (JJ)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0003-1807-8570

Michael P Morley (MP)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.

Justine Carl (J)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Alexis N Brumwell (AN)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Jeremy Katzen (J)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Katherine J Slovik (KJ)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.

Apoorva Babu (A)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.

Su Zhou (S)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Madison M Kremp (MM)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Katherine B McCauley (KB)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA, USA.
ORCID: 0000-0002-8817-7120

Shanru Li (S)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Joseph D Planer (JD)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Shah S Hussain (SS)

Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.

Xiaoming Liu (X)

Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
ORCID: 0000-0002-3902-9105

Rebecca Windmueller (R)

Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Yun Ying (Y)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Kathleen M Stewart (KM)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Michelle Oyster (M)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jason D Christie (JD)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Joshua M Diamond (JM)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

John F Engelhardt (JF)

Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
ORCID: 0000-0003-2389-9277

Edward Cantu (E)

Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Division of Cardiovascular Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Steven M Rowe (SM)

Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
ORCID: 0000-0001-9045-0133

Darrell N Kotton (DN)

Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA, USA.
The Pulmonary Center and Department of Medicine, Boston University and Boston Medical Center, Boston, MA, USA.
ORCID: 0000-0002-9604-8476

Harold A Chapman (HA)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-5280-5527

Edward E Morrisey (EE)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. emorrise@pennmedicine.upenn.edu.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. emorrise@pennmedicine.upenn.edu.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. emorrise@pennmedicine.upenn.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Human distal airways contain a multipotent...
questionsmedicales.fr › Appareil respiratoire › Poumon › Bronches › Bronchioles › Human distal airways contain a multipotent...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Développement embryonnaire et foetal › Développement embryonnaire › Lignage cellulaire › Human distal airways contain a multipotent...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Carnivora › Pinnipedia › Mustelidae › Furets › Human distal airways contain a multipotent...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Human distal airways contain a multipotent...
questionsmedicales.fr › Appareil respiratoire › Poumon › Human distal airways contain a multipotent...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Human distal airways contain a multipotent...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches multipotentes › Human distal airways contain a multipotent...
questionsmedicales.fr › Appareil respiratoire › Poumon › Alvéoles pulmonaires › Human distal airways contain a multipotent...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Broncho-pneumopathie chronique obstructive › Human distal airways contain a multipotent...