CAGE whole transcriptome differential expression analysis of acute effects of consumption level of caffeine on iPSC-derived neuronal cell culture.

Caffeine is a widely used central nervous system stimulant. Little is known about the effects of caffeine stimulation on global gene expression changes in the neurons. We conducted gene expression profiling on human neuronal/glia cell culture differentiated from iPSC-derived neuronal stem cells, stimulated with consumption levels of caffeine (3µM and 10µM), over 9 hours. We found dosage-dependent activation of immediate early genes after 1 hour. Neuronal projection development process was up-regulated and negative regulation of axon extension process was down-regulated at 3 h. In addition, extracellular matrix organization, response for wound healing, and regulation of immune system processes were dampened by caffeine at 3h. This study identified novel genes within the neuronal projection guidance pathways that respond to acute caffeine stimulation and suggests potential mechanisms for how caffeine acts on neurons.