Transcriptional alterations in the brain following Dot1l conditional knockout using the Emx1-Cre mouse line at embryonic day 16.5 [EmxDotRNAE16]

During cerebral cortex development, neural stem cells (NSCs) require precise spatiotemporal signals to acquire the correct cell identity at the exact moment. Even though epigenetic regulation plays a central role in cell fate decisions, the exact mechanisms remain elusive. Thus, we focus our research on the H3K79 methyltransferase DOT1L, a key player in cell fate decisions. Our group has shown that DOT1L prevents NSC premature differentiation by increasing expression of genes that regulate asymmetric cell division (Franz et al. 2019). Using cell-lineage tracing and pharmacological inhibition, we confirmed that when DOT1L is inhibited apical progenitors (APs) switch to symmetric neurogenic divisions in detriment of asymmetric self-renewal (Appiah et al. 2023). We now analyse conditional knockout (cKO) and control (WT) mice for DOT1L using Emx1-Cre line during cortical mid-neurogenesis (E14.5) using single cell RNA-seq to understand how the transcriptome changes. Overall design: Emx1Dot cKO and control mouse embryos were harvested at E16.5. The cerebral cortex was dissected, dissociated into a cell suspension and analyzed using scRNA-seq.