ECEESPE2025 Oral Communications Oral Communications 10: Pituitary, Neuroendocrinology and Puberty Part 2 (6 abstracts)
Unravelling the core regulatory network controlling stem cell fate in the anterior pituitary
Miriam Vazquez Segoviano 1 , Bence Kover 1 , Emily Lodge 2 , James Kaufman-Cook 1 , Yasmine Kemkem 1 , Olivia Sherwin 1 , Marika Charalambous 1,3 , Stuart Sealfon 4 , Frederique Ruf-Zamojski 5 & Cynthia Andoniadou 1,6
1King’s College London, London, United Kingdom; 2University College London, London, United Kingdom; 3Francis Crick Institute, London, United Kingdom; 4Icahn School of Medicine at Mount Sinai, New York, United States; 5Cedars-Sinai Medical Center, Los Angeles, United States; 6Technical University of Dresden Medical School, Dresden, Germany
JOINT710
The anterior pituitary is a primary endocrine organ responsible for orchestrating major physiological processes including growth, metabolism, reproduction and our response to stress through hormone secretion. This dynamic gland contains a tissue-specific population of stem cells marked by the expression of the transcription factor (TF) SOX2, which are required for homeostasis throughout life. Although pituitary stem cells (PSCs) are highly proliferative during early postnatal life, their regeneration capacity declines with age, remaining largely quiescent during adult homeostatic conditions as a long-lived population. Knowing the genetic mechanisms of stem cell regulation is necessary to enable their exploitation in regenerative approaches for pituitary disorders. Previous research has demonstrated a central role for YAP/TAZ signalling in PSCs to promote self-renewal and proliferation while repressing differentiation in vivo, thereby positioning YAP as a key component of PSC regulation, acting through TEAD TFs. We carried out single nuclei (sn) multiome sequencing of anterior pituitaries from an inducible YAP overexpression model, where overexpression of non-degradable mutant YAP protein instigates self-renewal of PSCs. snMultiome studies enable gene expression profiling and chromatin accessibility simultaneously from individual cells. Transcription factor fingerprinting analyses revealed Nuclear Factor I (NFI) A, NFIB, NFIC and NFIX TFs as highly relevant to PSC regulation. The NFI family of TFs are important for cell fate of stem cell populations in other tissues, yet their role or possible involvement in pituitary disease has not been previously investigated. Here, we characterise NFI expression in the murine and human pituitary gland and demonstrate in silico, in vitro and in vivo data supporting that NFIs, together with YAP/TEADs and SOX2 are a core regulatory network driving stem cell self-renewal in the anterior pituitary.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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