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Publication : Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration.

First Author  Penkala IJ Year  2021
Journal  Cell Stem Cell Volume  28
Issue  10 Pages  1775-1789.e5
PubMed ID  33974915 Mgi Jnum  J:321733
Mgi Id  MGI:6874755 Doi  10.1016/j.stem.2021.04.026
Citation  Penkala IJ, et al. (2021) Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration. Cell Stem Cell 28(10):1775-1789.e5
abstractText  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.
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