Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate

Kazushige Shiraishi; Parisha P. Shah; Michael P. Morley; Claudia Loebel; Garrett T. Santini; Jeremy Katzen; Maria C. Basil; Susan M. Lin; Joseph D. Planer; Edward Cantu; Dakota L. Jones; Ana N. Nottingham; Shanru Li; Fabian L. Cardenas-Diaz; Su Zhou; Jason A. Burdick; Rajan Jain; Edward E. Morrisey

doi:10.1016/j.cell.2023.02.010

Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate

Kazushige Shiraishi
, Parisha P. Shah
, Michael P. Morley
, Claudia Loebel
, Garrett T. Santini
, Jeremy Katzen
, Maria C. Basil
, Susan M. Lin
, Joseph D. Planer
, Edward Cantu
, Dakota L. Jones
, Ana N. Nottingham
, Shanru Li
, Fabian L. Cardenas-Diaz
, Su Zhou
, Jason A. Burdick
, Rajan Jain
, Edward E. Morrisey

Surgery

Research output: Contribution to journal › Article › peer-review

124 Scopus citations

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.

Original language	English
Pages (from-to)	1478-1492.e15
Journal	Cell
Volume	186
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2023.02.010
State	Published - Mar 30 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Funding

We thank E. Joyce, S. Nguyen, D. Liberti, K. Shen, K. McDaid, T. Yamamoto, T. Sakamoto, B. Kim, the Flow Cytometry Core Laboratory of Children’s Hospital of Philadelphia, and CDB Microscopy Core at the University of Pennsylvania for technical assistance. We also thank Dr. Jan Lammerding for providing DN-KASH plasmids. This research was supported by the National Institutes of Health ( HL152194 , HL132999 , HL134745 , HL148857 to E.E.M.; DP2HL147123 , HL148857 to R.J.; HL007586 to M.C.B., S.M.L., and J.D.P.; HL155821 to E.C.), National Science Foundation (CMMI-1548571 to R.J. and P.P.S.), Longfonds BREATH Consortium, Burroughs Wellcome Foundation (R.J.), the JSPS overseas research fellowship (K.S.), the fellowship of Uehara Memorial Foundation (K.S.), and the fellowship of Astellas Foundation for Research on Metabolic Disorders (K.S.).

Funders	Funder number
National Science Foundation Arctic Social Science Program	CMMI-1548571
National Institutes of Health (NIH)	HL007586, HL155821, HL134745, DP2HL147123, HL148857, HL132999, HL152194
Burroughs Wellcome Fund
Uehara Memorial Foundation
Japan Society for the Promotion of Science
Astellas Foundation for Research on Metabolic Disorders

Keywords

alveolar epithelial cell
biophysical forces
lamina-associated domain
lung
mechanotransduction

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2023.02.010

Cite this

Shiraishi, K., Shah, P. P., Morley, M. P., Loebel, C., Santini, G. T., Katzen, J., Basil, M. C., Lin, S. M., Planer, J. D., Cantu, E., Jones, D. L., Nottingham, A. N., Li, S., Cardenas-Diaz, F. L., Zhou, S., Burdick, J. A., Jain, R., & Morrisey, E. E. (2023). Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate. Cell, 186(7), 1478-1492.e15. https://doi.org/10.1016/j.cell.2023.02.010

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title = "Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate",

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.",

keywords = "alveolar epithelial cell, biophysical forces, lamina-associated domain, lung, mechanotransduction",

author = "Kazushige Shiraishi and Shah, \{Parisha P.\} and Morley, \{Michael P.\} and Claudia Loebel and Santini, \{Garrett T.\} and Jeremy Katzen and Basil, \{Maria C.\} and Lin, \{Susan M.\} and Planer, \{Joseph D.\} and Edward Cantu and Jones, \{Dakota L.\} and Nottingham, \{Ana N.\} and Shanru Li and Cardenas-Diaz, \{Fabian L.\} and Su Zhou and Burdick, \{Jason A.\} and Rajan Jain and Morrisey, \{Edward E.\}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = mar,

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doi = "10.1016/j.cell.2023.02.010",

language = "English",

volume = "186",

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Shiraishi, K, Shah, PP, Morley, MP, Loebel, C, Santini, GT, Katzen, J, Basil, MC, Lin, SM, Planer, JD, Cantu, E, Jones, DL, Nottingham, AN, Li, S, Cardenas-Diaz, FL, Zhou, S, Burdick, JA, Jain, R & Morrisey, EE 2023, 'Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate', Cell, vol. 186, no. 7, pp. 1478-1492.e15. https://doi.org/10.1016/j.cell.2023.02.010

TY - JOUR

T1 - Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate

AU - Shiraishi, Kazushige

AU - Shah, Parisha P.

AU - Morley, Michael P.

AU - Loebel, Claudia

AU - Santini, Garrett T.

AU - Katzen, Jeremy

AU - Basil, Maria C.

AU - Lin, Susan M.

AU - Planer, Joseph D.

AU - Cantu, Edward

AU - Jones, Dakota L.

AU - Nottingham, Ana N.

AU - Li, Shanru

AU - Cardenas-Diaz, Fabian L.

AU - Zhou, Su

AU - Burdick, Jason A.

AU - Jain, Rajan

AU - Morrisey, Edward E.

PY - 2023/3/30

Y1 - 2023/3/30

N2 - 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.

AB - 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.

KW - alveolar epithelial cell

KW - biophysical forces

KW - lamina-associated domain

KW - lung

KW - mechanotransduction

UR - https://www.scopus.com/pages/publications/85151403114

UR - https://www.scopus.com/pages/publications/85151403114#tab=citedBy

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M3 - Article

C2 - 36870331

AN - SCOPUS:85151403114

SN - 0092-8674

VL - 186

SP - 1478-1492.e15

JO - Cell

JF - Cell

IS - 7

ER -

Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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