A Latent Activated Olfactory Stem Cell State Revealed by Single Cell Transcriptomic and Epigenomic Profiling

The olfactory epithelium is one of the few regions of the nervous system that sustains neurogenesis throughout life. Its experimental accessibility makes it especially tractable for studying molecular mechanisms that drive neural regeneration after injury-induced cell death. In this study, we used single cell sequencing to identify major regulatory players in determining olfactory epithelial stem cell fate after acute injury. We combined gene expression and accessible chromatin profiles of individual lineage traced olfactory stem cells to predict transcription factor activity specific to different lineages and stages of recovery. We further identified a discrete stem cell state that appears poised for activation, characterized by accessible chromatin around wound response and lineage specific genes prior to their later expression in response to injury. Together these results provide evidence that a subset of quiescent olfactory epithelial stem cells are epigenetically primed to support injury-induced regeneration.