Transcriptional response of brain cell types to oxygen decline

Brain hypoxia is associated with a wide range of physiological and clinical conditions. Although oxygen is an essential constituent of maintaining brain functions, our understanding of how specific brain cell types globally respond and adapt to decreasing oxygen conditions is incomplete. In this study, we exposed mouse primary neurons, astrocytes, and microglia to normoxia and two hypoxic conditions and obtained genome-wide transcriptional profiles of the treated cells. Analysis of differentially expressed genes under conditions of reduced oxygen revealed a canonical hypoxic response shared among different brain cell types. In addition, we observed a higher sensitivity of neurons to oxygen decline, and dissected cell type-specific biological processes affected by hypoxia. Importantly, this study establishes novel gene modules associated with brain cells responding to oxygen deprivation and reveals a state of profound stress incurred by hypoxia. Overall design: To investigate the effect of oxygen decline on mouse brain cells we individually cultured to maturity mouse primary neurons, mouse primary astrocytes and mouse primary microglia and exposed them to different levels of oxygen for 8h. There were 2 sets of experiments per cell type: 5% vs 21% O2 ( 4 samples each-Experiment A) and 1% vs 21% O2 (4 samples each - Experiment B). We then performed gene expression profiling analysis on the RNA-seq from the 16 samples obtained per cell-type. Comparative gene expression profiling analysis of RNA-seq data per cell type at 1% vs 5% and 5% vs 21% O2.