Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration

Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cel...

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Veröffentlicht in:Cell stem cell 2021-10, Vol.28 (10), p.1775-1789.e5
Hauptverfasser: Penkala, Ian J., Liberti, Derek C., Pankin, Joshua, Sivakumar, Aravind, Kremp, Madison M., Jayachandran, Sowmya, Katzen, Jeremy, Leach, John P., Windmueller, Rebecca, Stolz, Katharine, Morley, Michael P., Babu, Apoorva, Zhou, Su, Frank, David B., Morrisey, Edward E.
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container_end_page 1789.e5
container_issue 10
container_start_page 1775
container_title Cell stem cell
container_volume 28
creator Penkala, Ian J.
Liberti, Derek C.
Pankin, Joshua
Sivakumar, Aravind
Kremp, Madison M.
Jayachandran, Sowmya
Katzen, Jeremy
Leach, John P.
Windmueller, Rebecca
Stolz, Katharine
Morley, Michael P.
Babu, Apoorva
Zhou, Su
Frank, David B.
Morrisey, Edward E.
description Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cell plasticity is a major and unappreciated mechanism that drives regeneration, beginning in the early postnatal period during alveolar maturation. Upon acute neonatal lung injury, AT1 cells reprogram into alveolar type 2 (AT2) cells, promoting alveolar regeneration. In contrast, the ability of AT2 cells to regenerate AT1 cells is restricted to the mature lung. Unbiased genomic assessment reveals that this previously unappreciated level of plasticity is governed by the preferential activity of Hippo signaling in the AT1 cell lineage. Thus, cellular plasticity is a temporally acquired trait of the alveolar epithelium and presents an alternative mode of tissue regeneration in the postnatal lung. [Display omitted] •Alveolar type 1 cells exhibit plasticity after neonatal and adult hyperoxic injury•YAP/TAZ actively maintain alveolar type 1 cell identity•Ectopic nuclear YAP is insufficient to induce type 2 to type 1 cell differentiation Penkala et al. investigate the effects of acute hyperoxic lung injury in neonatal and adult mice and demonstrate distinct, age-specific repair processes. They show that YAP/TAZ constrain type 1 cell identity and that the loss of these factors precipitates extensive alveolar type 1 to type 2 cell reprogramming.
doi_str_mv 10.1016/j.stem.2021.04.026
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source MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals
subjects Alveolar Epithelial Cells
alveolus
Animals
cellular plasticity
Hippo
Homeostasis
Lung
Mice
regeneration
Respiratory Mucosa
Signal Transduction
title Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration
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