Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration.
Hippo
alveolus
cellular plasticity
lung
regeneration
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
07 10 2021
07 10 2021
Historique:
received:
28
09
2020
revised:
11
03
2021
accepted:
21
04
2021
pubmed:
12
5
2021
medline:
26
10
2021
entrez:
11
5
2021
Statut:
ppublish
Résumé
Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cell plasticity is a major and unappreciated mechanism that drives regeneration, beginning in the early postnatal period during alveolar maturation. Upon acute neonatal lung injury, AT1 cells reprogram into alveolar type 2 (AT2) cells, promoting alveolar regeneration. In contrast, the ability of AT2 cells to regenerate AT1 cells is restricted to the mature lung. Unbiased genomic assessment reveals that this previously unappreciated level of plasticity is governed by the preferential activity of Hippo signaling in the AT1 cell lineage. Thus, cellular plasticity is a temporally acquired trait of the alveolar epithelium and presents an alternative mode of tissue regeneration in the postnatal lung.
Identifiants
pubmed: 33974915
pii: S1934-5909(21)00184-3
doi: 10.1016/j.stem.2021.04.026
pmc: PMC8500919
mid: NIHMS1703544
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1775-1789.e5Subventions
Organisme : NHLBI NIH HHS
ID : F31 HL140785
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087825
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL150226
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132349
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL134745
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL110942
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NICHD NIH HHS
ID : T32 HD083185
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL140129
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132999
Pays : United States
Organisme : NHLBI NIH HHS
ID : L40 HL129325
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152194
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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