ECE2018 Poster Presentations: Pituitary and Neuroendocrinology Pituitary - Basic (12 abstracts)
Activation of pituitary stem cells through modulation of the LATS/YAP/TAZ cascade
Emily Lodge 1 , John Russell 1 , Alice Santambrogio 1, , Paraskevi Xekouki 1 , Stefan Bornstein 1, & Cynthia Andoniadou 1,
1King’s College London, London, UK; 2TU Dresden, Dresden, Germany.
Pituitary stem cells (PSCs) expressing SOX2 persist throughout life, giving rise to all pituitary endocrine lineages. These cells are highly active at early postnatal stages but this potential declines with age, rendering them mostly inactive in adulthood. The LATS/YAP/TAZ signaling cascade can influence stem cell fate and activity in multiple tissues and we previously identified activity of this axis in the developing and postnatal pituitary. Using a series of genetic manipulations, we aimed to establish the functional role of this axis in PSC regulation in mouse. Conditional deletion of LATS1 kinase in the pituitary is sufficient to lead to accumulation of YAP/TAZ and subsequent anterior pituitary tumour formation. These non-functioning tumours are mostly composed of SOX2 positive cells and display histological features of carcinomas. Genetic experiments targeting only the SOX2 population, identify pituitary stem cells as the cell of origin of the tumours. Conditional expression of a constitutive-active form of YAP in the pituitary does not lead to tumour formation, revealing that YAP alone is not sufficient to mediate this phenotype. However, it is sufficient to drive expansion of the SOX2 pituitary stem cell pool at postnatal stages and to reinstate their activation. Together, out data show a crucial role of the LATS/YAP/TAZ axis in regulation of the pituitary stem cell pool, an important step toward future regenerative approaches.
Volume 56
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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