Effect of D-serine on gene expression in Neuro2a cells

Serine metabolism provides essential metabolites for cellular growth and proliferation, and also produces neurotransmitters. However, how serine metabolism coordinates with functional development of neurons remains unclear. We report neurotransmitter D-serine inhibit growth of immature cells. Metabolomic analysis of neural progenitors revealed that D-serine decreases glycine synthesis thereby diminishes one-carbon metabolism, in which L-serine is a crucial carbon donor. D-serine inhibits one-carbon metabolism by competing transport of cytosolic L-serine to mitochondria, which restrains proliferation and triggers apoptosis of neural progenitors as well as neural tumor cells, but not mature neurons, in vitro and ex vivo. This RNA-seq data supports the idea that D-serine inhibits polarization and growth/proliferation of immature neurons and further indicate that immature neurons counteracts D-serine-induced cellular stress through enhancing mitochondrial function, including energy synthesis. Overall design: Neuro2a cells were cultured in D-MEM with 10% FBS. The medium was changed to D-MEM(-SG) including 10% FBS with or without 5 mM D-serine. Cells were harvested in Trizol after 18 hours of incubation at 37 °C in a CO2 incubator. RNA was extracted from cells according to the manufacture's protocol. mRNA libraries of each samples were prepared using a TruSeq Stranded mRNA library Kit (Illumina, San Diego, CA) according to the manufactures' protocol and paired end sequences were read by NovaSeq (Illumina).