Preventable ATII Proliferation after Hyperoxia: The "Tempo" of Folate Metabolism in the Neonatal Lung

Eldredge discusses the paper by Yee et al which identifies a novel--and targetable--mechanism by which hyperoxia causes atypical proliferation of ATII cells in the newborn mouse lung. The authors demonstrate that an early and aberrant wave of ATII cell proliferation (PN1-4) after neonatal hyperoxia exposure is associated with genetic programs directing serine synthesis and one-carbon-coupled folate metabolism. These metabolic pathways affect cell proliferation through multiple mechanisms, nicely outlined by the authors to include redox defense, epigenetic maintenance, and biosynthesis. They also show that these gene expression pathways were also associated with the normal wave of postnatal ATII proliferation that peaks at PN7.