ArticleCell2023
Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate.
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Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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85 citing papers in PubMed, 116 citations in OpenAlex.
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- Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 1 country.
Kazushige ShiraishiDepartment 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 ShahDepartment 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 MorleyDepartment 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 LoebelDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA.
Garrett T SantiniDepartment 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 KatzenDepartment 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 BasilDepartment 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 LinDepartment 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 PlanerDepartment 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 CantuPenn-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 JonesDepartment 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 NottinghamDepartment 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 LiDepartment 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-DiazDepartment 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 ZhouDepartment 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 BurdickDepartment 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 JainDepartment 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 MorriseyDepartment 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.
University of Pennsylvania · USPenn Center for AIDS Research · USUniversity of Colorado Boulder · US
Funding
Institutional Clinical and Translational Science AwardKL2TR001879 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MEAGHER, EMMA ANNE · 2016 to 2025
$13.7MTRAINING IN PULMONARY IMMUNOLOGYT32HL007586 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 1985 to 2025
$8.8MEditing Alveolar Progenitor Cells for Correction of Monogenic DiseaseU01HL134745 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTON, DARRELL N., MORRISEY, EDWARD E · 2016 to 2022
$8.3MMolecular pathways controlling alveolar epithelial remodeling in development and regenerationR01HL132999 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2016 to 2023
$4.6MMulti-modal characterization of three human lung niches at the single cell levelU01HL148857 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2019 to 2023
$4.4MObjective Lung Assessment Tools for Improved Organ Use in Lung TransplantationR01HL155821 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI CANTU, EDWARD · 2021 to 2025
$3.0MDeciphering Nuclear Lamina-Chromatin Organization in Cellular Competence and Cardiac DevelopmentDP2HL147123 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI JAIN, RAJAN · 2018 to 2018
$2.4MDevelopmental pathways regulating adult lung quiescenceR01HL132349 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2016 to 2019
$2.3MTranscriptional Regulation of Lung Alveolar RegenerationR01HL152194 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2021 to 2024
$2.3MMolecular regulation of cell fate and progenitor function in the distal human respiratory airwaysK08HL163398 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Maria Ciocca Basil · 2022 to 2026
$834kNCATS NIH HHS KL2 TR001879NHLBI NIH HHS DP2 HL147123NHLBI NIH HHS K08 HL163398NHLBI NIH HHS R01 HL132349NHLBI NIH HHS R01 HL132999NHLBI NIH HHS R01 HL152194NHLBI NIH HHS R01 HL155821NHLBI NIH HHS T32 HL007586NHLBI NIH HHS U01 HL134745NHLBI NIH HHS U01 HL148857
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.
Indexed as
Alveolar Epithelial CellsMechanotransduction, CellularCell DifferentiationCells, CulturedLungRespirationalveolar epithelial cellbiophysical forceslamina-associated domainlungmechanotransduction
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