The Oxygen Environment at Birth Specifies the Population of Alveolar Epithelial Stem Cells in the Adult Lung

Stem Cells
Min YeeMichael A O'Reilly

Abstract

Alveolar epithelial type II cells (AEC2) maintain pulmonary homeostasis by producing surfactant, expressing innate immune molecules, and functioning as adult progenitor cells for themselves and alveolar epithelial type I cells (AEC1). How the proper number of alveolar epithelial cells is determined in the adult lung is not well understood. Here, BrdU labeling, genetic lineage tracing, and targeted expression of the anti-oxidant extracellular superoxide dismutase in AEC2s are used to show how the oxygen environment at birth influences postnatal expansion of AEC2s and AEC1s in mice. Birth into low (12%) or high (≥60%) oxygen stimulated expansion of AEC2s through self-renewal and differentiation of the airway Scgb1a1 + lineage. This non-linear or hormesis response to oxygen was specific for the alveolar epithelium because low oxygen stimulated and high oxygen inhibited angiogenesis as defined by changes in V-cadherin and PECAM (CD31). Although genetic lineage tracing studies confirmed adult AEC2s are stem cells for AEC1s, we found no evidence that postnatal growth of AEC1s were derived from self-renewing Sftpc + or the Scbg1a1 + lineage of AEC2s. Taken together, our results show how a non-linear response to oxygen at birth promote...Continue Reading

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Citations

Apr 12, 2016·Frontiers in Pediatrics·Daniel ImBarbara Driscoll
Mar 2, 2017·American Journal of Respiratory Cell and Molecular Biology·Michael A O'Reilly
Dec 15, 2016·American Journal of Respiratory Cell and Molecular Biology·Min YeeMichael A O'Reilly
Apr 1, 2017·American Journal of Respiratory Cell and Molecular Biology·Andrew E Vaughan, Harold A Chapman
Jan 10, 2017·Disease Models & Mechanisms·Claudio NardielloRory E Morty
Nov 17, 2017·Cell Cycle·Mei-Yao HeXuesong Yang
Feb 6, 2017·Pediatric Pulmonology·Tanbir NajranaJuan Sanchez-Esteban
Feb 6, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yves DonatiConstance Barazzone-Argiroffo
Jul 18, 2020·Nature Communications·Maximilian StrunzHerbert B Schiller
Mar 25, 2021·Free Radical Biology & Medicine·Collynn F WoellerMichael A O'Reilly
May 21, 2020·Cell Metabolism·C Hai LyJames G Ryall
May 18, 2021·Frontiers in Cell and Developmental Biology·Yu XuefeiFu Jianhua
Jul 30, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Andrew M DylagMichael A O'Reilly

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