Polycomb repressive complex 2 in adult hair follicle stem cells is dispensable for hair regeneration

Author summaryHair follicle stem cells (HFSCs) have the incredible capacity to cycle through quiescence and activation to fuel the production of hair follicles throughout the life of an organism. During the onset of hair growth, HFSCs undergo transient activation to proliferate but quickly revert to their quiescent state for the remaining of the hair cycle phases. This balance between HFSC activation and quiescence is maintained by establishing a specific transcriptional landscape; however, very little is known about how chromatin-modifying factors, critical regulators of gene transcription, control adult HFSC function. Prior genome mapping studies had shown that H3K27me3, the chromatin mark mediated by Polycomb Repressive Complex 2 (PRC2), is dynamic between quiescent and activated HFSCs, suggesting that transcriptional changes associated with H3K27me3 might be critical for proper HFSC function. Despite this correlation, functional in vivo studies elucidating the role of PRC2 in adult HFSCs were lacking. In this study, we show that ablation of PRC2 in the adult HFSCs leads to modest transcriptional changes that are insufficient to alter HFSC fate or function to have physiologically relevant effects, indicating that other chromatin regulatory mechanisms could be safeguarding adult HFSC function and identity. Hair follicle stem cells (HFSCs) are multipotent cells that cycle through quiescence and activation to continuously fuel the production of hair follicles. Prior genome mapping studies had shown that tri-methylation of histone H3 at lysine 27 (H3K27me3), the chromatin mark mediated by Polycomb Repressive Complex 2 (PRC2), is dynamic between quiescent and activated HFSCs, suggesting that transcriptional changes associated with H3K27me3 might be critical for proper HFSC function. However, functional in vivo studies elucidating the role of PRC2 in adult HFSCs are lacking. In this study, by using in vivo loss-of-function studies we show that, surprisingly, PRC2 plays a non-instructive role in adult HFSCs and loss of PRC2 in HFSCs does not lead to loss of HFSC quiescence or changes in cell identity. Interestingly, RNA-seq and immunofluorescence analyses of PRC2-null quiescent HFSCs revealed upregulation of genes associated with activated state of HFSCs. Altogether, our findings show that transcriptional program under PRC2 regulation is dispensable for maintaining HFSC quiescence and hair regeneration.