Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate.


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
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.e15

Subventions

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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Auteurs

Kazushige Shiraishi (K)

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.

Parisha P Shah (PP)

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; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

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.

Claudia Loebel (C)

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA.

Garrett T Santini (GT)

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; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 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.

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; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.

Susan M Lin (SM)

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.

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.

Dakota L Jones (DL)

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.

Ana N Nottingham (AN)

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.

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.

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.

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; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jason A Burdick (JA)

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA; BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, USA.

Rajan Jain (R)

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; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Edward E Morrisey (EE)

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; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: emorrise@pennmedicine.upenn.edu.

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Classifications MeSH