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Gonzalez-Meljem, Jose Mario; Haston, Scott; Carreno, Gabriela; Apps, John R.; Pozzi, Sara; Stache, Christina; Kaushal, Grace; Virasami, Alex; Panousopoulos, Leonidas; Mousavy-Gharavy, Seyedeh Neda; Guerrero, Ana; Rashid, Mamunur; Jani, Nital; Goding, Colin R.; Jacques, Thomas S.; Adams, David J.; Gil, Jesus; Andoniadou, Cynthia L.; Martinez-Barbera, Juan Pedro

Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma

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  • Medientyp: E-Artikel
  • Titel: Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma
  • Beteiligte: Gonzalez-Meljem, Jose Mario; Haston, Scott; Carreno, Gabriela; Apps, John R.; Pozzi, Sara; Stache, Christina; Kaushal, Grace; Virasami, Alex; Panousopoulos, Leonidas; Mousavy-Gharavy, Seyedeh Neda; Guerrero, Ana; Rashid, Mamunur; Jani, Nital; Goding, Colin R.; Jacques, Thomas S.; Adams, David J.; Gil, Jesus; Andoniadou, Cynthia L.; Martinez-Barbera, Juan Pedro
  • Erschienen: Springer Science and Business Media LLC, 2017
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-017-01992-5
  • ISSN: 2041-1723
  • Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2− cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis. We show that expression of oncogenic β-catenin in Hesx1+ embryonic precursors also results in stem cell clusters and paracrine tumours. We reveal that human and mouse clusters are analogous and share a common signature of senescence and SASP. Finally, we show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potential. Together, we provide evidence that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in vivo in an age-dependent fashion.</jats:p>
  • Zugangsstatus: Freier Zugang