Loss of PRC1 activity in different stem cell compartments activates a common transcriptional program with cell-type dependent outcome

Polycomb Repressive Complexes (PRCs) are evolutionary-conserved multiprotein complexes that maintain transcriptional repression during development and differentiation to establish and preserve cell identity. Through the enzymatic activity of the subunits Ring1A and Ring1B, PRC1 monoubiquitinates histone H2A on lysine 119, promoting nucleosome compaction. We recently described a fundamental role of PRC1 in preserving intestinal stem cells identity through the inhibition of non-lineage specific transcription factors. To gain more insight into the role of PRC1 in adult stem cell maintenance, we have now investigated its role in LGR5+ hair follicle stem cells during physiological regeneration. We show that PRC1 depletion in LGR5+ cells severely affects hair regeneration. Differently from what we described for ISCs, the release of target transcriptional repression upon loss of PRC1 activity induces the ectopic activation of an epidermal-specific program. Our data support a general role of PRC1 in preserving cell identity that is shared between different stem cell compartments. However, we propose that the final outcome of the ectopic activation of non-lineage specific transcription factors observed upon loss of PRC1 in stem cells is largely context-dependent and likely related to the transcription factors repertoire and the specific epigenetic landscape of the different cellular compartments.