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

Abstract

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.

Epigenetic regulation of embryonic ectoderm development in stem cell differentiation and transformation during ontogenesis

“…Premature epidermal barrier development, ectopic Merkel cell formation, and postnatal hair follicle developmental hurdle Dauber et al 129 Decreases the proliferation of hair follicle progenitor cells Perdigoto et al 130 Cannot induce HFSCs activation or fate switch; epidermal pigmentation Cohen et al 131 Flora et al 132 Li et al 133 Haematopoiesis Haematopoiesis defects Lessard et al 141 Increasing susceptibility to hematologic malignancies of EED heterozygous mutants Majewski et al 144 Neonatal pale and hypocellular Xie et al 138 Perturbs the BM HSCs differentiation into restricted lineage progenitor cells Yu et al 112 Ueda et al 143…”

“…Loss of both PRC1/2 complexes in EpSCs leads to the key epidermal lineage TFs such as P63 and SATB1 being significantly down‐regulated in EpSCs, indicating functional redundancy between PRC1 and PRC2 in the maintenance of epidermal stem cell identity. Moreover, EED absences in adult hair follicle stem cells (HFSCs) cannot induce HFSCs activation or fate switch 132 . In contrast, loss of EED function in adult epidermal stem cells results in epidermal pigmentation 133 .…”

“…Moreover, EED absences in adult hair follicle stem cells (HFSCs) cannot induce HFSCs activation or fate switch. 132 In contrast, loss of EED function in adult epidermal stem cells results in epidermal pigmentation. 133 These studies highlight the functional complexity of EED in different cell lineages of the developing and adult epidermis.…”

LSD1 interacting with HSP90 promotes skin wound healing by inducing metabolic reprogramming of hair follicle stem cells through the c‐MYC/LDHA axis

“…26 In recent years, some studies have shown that lysine methyltransferases and lysine demethylases exert functions in the proliferation and differentiation of HFSCs. [27][28][29] Therefore, in order to screen key histone methylation-related enzymes that play a role in the proliferation and differentiation of HFSCs, we downloaded the RNA sequencing dataset GSE109574 from the GEO database, which contained 3 HFSCs in quiescent period and 4 HFSCs in growth period. To further identify the key genes involved in HFSC growth and wound healing, we performed differential analysis on the RNA sequencing dataset GSE89928 containing HFSCs samples from 5 controls and 2 skin-injured mice.…”

Polycomb Directed Cell Fate Decisions in Development and Cancer

“…However, despite the role of PRC2 in hair follicle self-renewal, as previously discussed, genome-wide transcriptional studies in adult hair follicular stem cells have demonstrated that PRC2 does not alter the homeostatic hair cycle, and in quiescent cells does not promote fate switch. Therefore, PRC2 and H3K27me3 play a non-instructive role in this context, and there may be redundant or alternate mechanisms acting to preserve hair follicle stem cell functions and fate maintenance [ 178 ].…”