Alveolar epithelial type 2 (AT2) cells are an adult lung stem cell. Oxidative stress, mitogens, and cytokines affect their proliferation through poorly understood mechanisms. We previously showed in mice how neonatal hyperoxia between postnatal days (PND) 0-4 accelerates AT2 proliferation that normally takes place on PND7. Here, RNA-seq analysis of revealed neonatal hyperoxia stimulates expression of the mitochondrial-specific methylenetetrahydrofolate dehydrogenase (Mthfd) 2 and other genes involved in serine synthesis and one carbon-coupled folate metabolism. While MTHFD2 is important for embryonic development and proliferation of cancer cells, it is non-essential after birth. However, Mthf2 mRNA and other enzymes in serine and folate metabolism were highly expressed when AT2 cells proliferate on PND7. They were nearly undetectable in adult AT2 cells, but re-expressed when AT2 cells proliferated in response to fibroblast growth factor (FGF) 7 or during alveolar regeneration. Suppressing Mthfd2 or phosphoglycerate dehydrogenase (Phgdh) used to generate serine blocked FGF7-dependent proliferation of AT2 cells. SOURCE: Andrew McDavid University of Rochester

Pluto Bioinformatics

GSE140915: Type II lung cells in young mice exposed to differing levels of oxygen