biostudies-literatureWalko GMedical Research CouncilWellcome TrustBiotechnology and Biological Sciences Research Council14744https://www.ebi.ac.uk/biostudies/studies/S-EPMC5376649biostudies-literatureUnknown8Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reNature communicationsA genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells.PMC5376649G1100073BB/M007219/1Liakath-Ali KLichtenberger BMWatt FMWalko GPisco AOLogtenberg MViswanathan PWoodhouse STelerman SBMishra AQuist SRRenz LMRognoni EDonati GfalseA genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells.Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in re2017-01-01T00:00:00Z2017 Mar2026-05-30T10:54:15.937Z2019-03-27T02:40:09ZS-EPMC53766492833249810.1038/ncomms14744