Polycomb repressive complex 2 regulates basal cell fate during adult olfactory neurogenesis

Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable to injury yet essential for olfaction. Multipotent olfactory basal stem cells are activated by damage, although mechanisms regulating lineage decisions are not understood. Using mouse lesion models, we focused on defining the role of Polycomb repressive complexes (PRCs) in olfactory neurogenesis. PRC2 has a well-established role in developing tissues, orchestrating transcriptional programs via chromatin modification. PRC2 proteins are expressed in olfactory globose basal cells (GBCs) and nascent neurons. Conditional PRC2 loss perturbs lesion-induced neuron production, accompanied by altered histone modifications and misexpression of lineage-specific transcription factors in GBCs. De-repression of Sox9 in PRC2-mutant GBCs is accompanied by increased Bowman’s gland production, defining an unrecognized role for PRC2 in regulating gland versus neuron cell fate. Our findings support a model for PRC2-dependent mechanisms promoting sensory neuronal differentiation in an adult neurogenic niche. [Display omitted] •PRC2 proteins are expressed in olfactory basal cells in normal and injured conditions•H3K27me3 marks genes active in neurogenesis and differentiation in olfactory basal cells•PRC2 regulates choice between neuronal and non-neuronal lineages Ko et al. identified PRC2 as a mechanism regulating neurogenesis in the adult olfactory epithelium. PRC2-mutant olfactory basal cells lack key H3K27me3 marks and de-repress non-neural transcriptional programs, including Sox9. Lineage-traced Eed-deficient basal cells produce fewer neurons and more non-neuronal cells, including Bowman’s glands, establishing PRC2 as an epigenetic mechanism regulating olfactory neuron versus Bowman’s gland lineage choice.