Journal article
Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate
Cell, Vol.186(7), pp.1478-1492.e15
03/30/2023
DOI: 10.1016/j.cell.2023.02.010
PMCID: PMC10065960
PMID: 36870331
Abstract
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.
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•Mechanotransduction is a key feature of alveolar type 1 (AT1) cells in the lung•Actin remodeling and integrin signaling regulate AT1 and AT2 cell fate transitions•Physical blockade of respiratory movement leads to loss of AT1 cell identity•Nuclear lamina-chromatin interactions determine alveolar epithelial cell fate
Forces elicited by respiration actively induce changes in nuclear lamina-chromatin interactions to maintain alveolar type 1 (AT1) cell identity and restrict these cells from reprogramming into AT2 cells.
Details
- Title: Subtitle
- Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate
- Creators
- Kazushige Shiraishi - University of PennsylvaniaParisha P. Shah - University of PennsylvaniaMichael P. Morley - University of PennsylvaniaClaudia Loebel - University of PennsylvaniaGarrett T. Santini - University of PennsylvaniaJeremy Katzen - University of PennsylvaniaMaria C. Basil - University of PennsylvaniaSusan M. Lin - University of PennsylvaniaJoseph D. Planer - University of PennsylvaniaEdward Cantu - University of PennsylvaniaDakota L. Jones - University of PennsylvaniaAna N. Nottingham - University of PennsylvaniaShanru Li - University of PennsylvaniaFabian L. Cardenas-Diaz - University of PennsylvaniaSu Zhou - University of PennsylvaniaJason A. Burdick - University of Colorado BoulderRajan Jain - University of PennsylvaniaEdward E. Morrisey - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.186(7), pp.1478-1492.e15
- DOI
- 10.1016/j.cell.2023.02.010
- PMID
- 36870331
- PMCID
- PMC10065960
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 03/30/2023
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984949264102771
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