Jing Qiu, Jamie McQueen, Bilada Bilican, Owen Dando, Matt Livesey, Ghazal Haghi, Timothee Cezard, Karen Burr, Rickie Patani, Rinku Rajan, Olivia Sheppard, Peter C. Kind, Ian Simpson, Victor L.J. Tybulewicz, David J. A. Wyllie, Karim Gharbi, Elizabeth Fisher, Siddharthan Chandran and Giles E. Hardingham University of Edinburgh and UCLMany neuronal processes including development, survival and plasticity, rely on activity-dependent changes to the transcriptome. Whilst much has been learnt from studies of rodent neurons, the degree of conservation between rodent and human neurons is unknown. Using RNA-seq, we compared the activity-dependent transcriptome of developing cortical-patterned human embroyonic stem cell-derived neurons with that of primary- or stem cell-derived mouse cortical neurons in response to L-type Ca2+ channel activation. Although activity-dependent gene-responsiveness showed little dependence on developmental stage or origin, significant species-dependent differences were observed. Species-specific gene induction was confirmed using mouse cortical neurons from Tc1 mice, which carry human chromosome-21, allowing for direct comparison of mouse and human gene expression from the same neurons. Analysis of the promoter regions of uniquely regulated genes revealed human-specific activity-responsive AP-1 sites. These findings support the use of human neuronal systems for probing transcriptional responses to physiological stimuli or indeed pharmaceutical agents.Funded by: the MRC, the Wellcome Trust, the BBSRC and the Royal Society. This article was published on 2024-12-13
