Analysis and pharmacological modulation of senescence in human epithelial stem cells
| العنوان: | Analysis and pharmacological modulation of senescence in human epithelial stem cells |
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| المؤلفون: | Vanessa Barbaro, Antonio Orvieto, Gualtiero Alvisi, Marina Bertolin, Filippo Bonelli, Thomas Liehr, Tigran Harutyunyan, Stefanie Kankel, Gordana Joksic, Stefano Ferrari, Elena Daniele, Diego Ponzin, Daniela Bettio, Leonardo Salviati, Enzo Di Iorio |
| المصدر: | Journal of Cellular and Molecular Medicine, 26 (14) |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | DAPT (γ-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine T-butyl ester), p63, Stem Cells, Cleft Lip, EEC syndrome, RNAseq, lifespan, self-renewal, stem cells, Humans, Platelet Aggregation Inhibitors, Cleft Palate, Ectodermal Dysplasia, Cell Biology, N-[N-(3, Molecular Medicine, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine T-butyl ester) |
| الوصف: | Human epithelial stem cells (ESCs) are characterized by long-term regenerative properties, much dependent on the tissue of origin and varying during their lifespan. 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-ectodermal dysplasia-clefting 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 (gamma-secretase inhibitor; N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine T-butyl ester). All cells were able to differentiate in vitro but exhibited variable self-renewal 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- or down-regulated during their lifetime, thus allowing to identify druggable gene networks and off-the-shelf 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. Journal of Cellular and Molecular Medicine, 26 (14) ISSN:1582-1838 ISSN:1582-4934 |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| تدمد: | 1582-1838 1582-4934 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f0df4f682093bbba1c4617b3b487b8e http://hdl.handle.net/11577/3455390 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8f0df4f682093bbba1c4617b3b487b8e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15821838 15824934 |
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