Silvia Pivetti

Cell identity has to be maintained throughout life and its deregulation leads to several pathologies, primarily cancer. Polycomb Repressive Complex 1 (PRC1) are evolutionary-conserved multiprotein complexes that through the deposition of a Ubiquitin molecule on lysine 119 of histone H2A promotes transcriptional repression. We described the fundamental role of PRC1 in preserving intestinal stem cells identity through the inhibition of non-lineage specific transcription factors. However, tissue context plays a critical role in protein function, leading to the possibility that PRC1 could work differently among tissues. To investigate PRC1 role in adult stem cell maintenance, we examined its role in hair follicle stem cells during regeneration. We elucidated a general role of PRC1 in stem cell identity maintenance, accomplished through the regulation of the same targets. However, differently from intestine, PRC1 loss in the hair follicle leads to the activation of a specific epidermal program, showing that the pool of transcription factors present in different stem cell population alters the transcriptional outcome of PRC1 loss.

PRC1 is composed by several subunits that define different biochemical sub-complexes specified by 6 different mutually exclusive PCGF proteins (PCGF1-6). Their role in embryonic development is widely studied, however their involvement in adult tissue maintenance is still obscure. Exploiting different PCGFs conditional knock out mouse models we aim to address the specific sub complexes roles in tissue homeostasis maintenance, in order to define their contribution in the phenotypic outcome observed in PRC1 loss of function intestinal and hair follicle LGR5 stem cells.