Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate.
alveolar epithelial cell
biophysical forces
lamina-associated domain
lung
mechanotransduction
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
30 03 2023
30 03 2023
Historique:
received:
15
06
2022
revised:
21
12
2022
accepted:
07
02
2023
pmc-release:
30
03
2024
medline:
4
4
2023
pubmed:
5
3
2023
entrez:
4
3
2023
Statut:
ppublish
Résumé
Lungs undergo mechanical strain during breathing, but how these biophysical forces affect cell fate and tissue homeostasis are unclear. We show that biophysical forces through normal respiratory motion actively maintain alveolar type 1 (AT1) cell identity and restrict these cells from reprogramming into AT2 cells in the adult lung. AT1 cell fate is maintained at homeostasis by Cdc42- and Ptk2-mediated actin remodeling and cytoskeletal strain, and inactivation of these pathways causes a rapid reprogramming into the AT2 cell fate. This plasticity induces chromatin reorganization and changes in nuclear lamina-chromatin interactions, which can discriminate AT1 and AT2 cell identity. Unloading the biophysical forces of breathing movements leads to AT1-AT2 cell reprogramming, revealing that normal respiration is essential to maintain alveolar epithelial cell fate. These data demonstrate the integral function of mechanotransduction in maintaining lung cell fate and identifies the AT1 cell as an important mechanosensor in the alveolar niche.
Identifiants
pubmed: 36870331
pii: S0092-8674(23)00127-7
doi: 10.1016/j.cell.2023.02.010
pmc: PMC10065960
mid: NIHMS1875779
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
1478-1492.e15Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL134745
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132999
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155821
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132349
Pays : United States
Organisme : NHLBI NIH HHS
ID : DP2 HL147123
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152194
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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