Distinct fibroblasts lineages are defined by global H3K27 methyl marks. Mus musculus

Fibroblasts subpopulations with distinct functions and identities have been identified in the skin. Lineage-tracing experiments have elegantly demonstrated when the heterogeneity is determined but how heterogeneity is established and maintained remains elusive. By profiling a variety of histone methylation marks in the skin we identified a striking heterogeneity of H3K27 methyl-marks within different subpopulations of dermal cells. Isolation of fibroblast subpopulations using established markers revealed high levels of PRC2 complex proteins in the papillary dermis with less abundance in the reticular layer. Molecular analysis using RNA and ChIP-Seq revealed that the marks deposited by PRC2 complex inhibit preadipogenic gene expression in papillary cells. Accordingly in vitro or in vivo inhibition of methyltransferase activity resulted in delayed wound healing and differentiation of papillary fibroblasts to preadipogenic reticular cells. These findings shed light on the active mechanisms that are operated by repressive Polycomb complex members to maintain the cellular identity in dermal tissue.