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We analysed such variables in cultures of ESCs isolated from the skin, conjunctiva, limbus and oral mucosa of healthy donors and patients affected by ectrodactyly\u2010ectodermal dysplasia\u2010clefting syndrome, a rare genetic disorder caused by mutations in the p63 gene. We cultured cells until exhaustion in the presence or in the absence of DAPT (\u03b3\u2010secretase inhibitor; N\u2010[N\u2010(3, 5\u2010difluorophenacetyl)\u2010L\u2010alanyl]\u2010S\u2010phenylglycine T\u2010butyl ester). All cells were able to differentiate in vitro but exhibited variable self\u2010renewal potential. In particular, cells carrying p63 mutations stopped prematurely, compared with controls. Importantly, administration of DAPT significantly extended the replicative properties of all stem cells under examination. RNA sequencing analysis revealed that distinct sets of genes were up\u2010 or down\u2010regulated during their lifetime, thus allowing to identify druggable gene networks and off\u2010the\u2010shelf compounds potentially dealing with epithelial stem cell senescence. These data will expand our knowledge on the genetic bases of senescence and potentially pave the way to the pharmacological modulation of ageing in epithelial stem cells.<\/jats:p>","DOI":"10.1111\/jcmm.17434","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T05:44:50Z","timestamp":1655358290000},"page":"3977-3994","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Analysis and pharmacological modulation of senescence in human epithelial stem cells"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8760-2343","authenticated-orcid":false,"given":"Vanessa","family":"Barbaro","sequence":"first","affiliation":[{"name":"Fondazione Banca degli Occhi del Veneto  Venice Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Orvieto","sequence":"additional","affiliation":[{"name":"Department of Computer Science ETH Zurich 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