RT Journal Article
SR Electronic
T1 Lung injury induces alveolar type 2 cell hypertrophy and polyploidy with implications for repair and regeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.10.455833
DO 10.1101/2021.08.10.455833
A1 Anthea Weng
A1 Mariana Maciel-Herrerias
A1 Satoshi Watanabe
A1 Lynn Welch
A1 Annette S. Flozak
A1 Rogan Grant
A1 Raul Piseaux Aillon
A1 Laura Dada
A1 Seung Hye Han
A1 Monique Hinchcliff
A1 Alexander Misharin
A1 GR Scott Budinger
A1 Cara J. Gottardi
YR 2022
UL http://biorxiv.org/content/early/2022/01/11/2021.08.10.455833.abstract
AB Epithelial polyploidization post-injury is a conserved phenomenon, recently shown to improve barrier restoration during wound healing. Whether lung injury can induce alveolar epithelial polyploidy is not known. We show that bleomycin injury induces AT2 cell hypertrophy and polyploidy. AT2 polyploidization is also seen in short term ex vivo cultures, where AT2-to-AT1 trans-differentiation is associated with substantial binucleation due to failed cytokinesis. Both hypertrophic and polyploid features of AT2 cells can be attenuated by inhibiting the integrated stress response (ISR) using the small molecule ISRIB. These data suggest that AT2 hypertrophic growth and polyploidization may be a feature of alveolar epithelial injury. As AT2 cells serve as facultative progenitors for the distal lung epithelium, a propensity for injury-induced binucleation has implications for AT2 self-renewal and regenerative potential upon reinjury, which may benefit from targeting the ISR.Competing Interest StatementThe authors have declared no competing interest.