Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate,Cell

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Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate
Cell ( IF 45.5 ) Pub Date : 2023-03-03 , DOI: 10.1016/j.cell.2023.02.010
Kazushige Shiraishi ₁ , Parisha P Shah ₂ , Michael P Morley ₃ , Claudia Loebel ₄ , Garrett T Santini ₂ , Jeremy Katzen ₁ , Maria C Basil ₃ , Susan M Lin ₁ , Joseph D Planer ₁ , Edward Cantu ₅ , Dakota L Jones ₁ , Ana N Nottingham ₁ , Shanru Li ₁ , Fabian L Cardenas-Diaz ₁ , Su Zhou ₆ , Jason A Burdick ₇ , Rajan Jain ₂ , Edward E Morrisey ₈

Affiliation

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

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.

中文翻译：

由呼吸介导的生物物理力维持肺泡上皮细胞的命运

肺部在呼吸过程中承受机械应变，但这些生物物理力如何影响细胞命运和组织稳态尚不清楚。我们发现，通过正常呼吸运动的生物物理力可积极维持肺泡 1 型 (AT1) 细胞身份，并限制这些细胞在成人肺中重编程为 AT2 细胞。 AT1 细胞命运通过 Cdc42 和 Ptk2 介导的肌动蛋白重塑和细胞骨架应变维持稳态，这些途径的失活会导致快速重编程为 AT2 细胞命运。这种可塑性会诱导染色质重组和核纤层-染色质相互作用的变化，从而区分 AT1 和 AT2 细胞身份。卸载呼吸运动的生物物理力量会导致 AT1-AT2 细胞重新编程，这表明正常呼吸对于维持肺泡上皮细胞的命运至关重要。这些数据证明了机械转导在维持肺细胞命运中的整体功能，并将 AT1 细胞确定为肺泡微环境中重要的机械传感器。

更新日期：2023-03-03

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