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Endocrine Abstracts (2021) 73 OC1.2 | DOI: 10.1530/endoabs.73.OC1.2

ECE2021 Oral Communications Oral Communications 1: Adrenal and Cardiovascular Endocrinology (6 abstracts)

YAP/TAZ signaling is involved in the regulation of adrenocortical progenitors in stress

Ilona Berger1, Alice Santambrogio1, 2, Stefan Bornstein1, 3, Cynthia L. Andoniadou1, 2 & CharlotteSteenblock1


1University Hospital Carl Gustav Carus Dresden, Department of Internal Medicine III, Dresden, Germany; 2King’s College London - Guy’s Campus, Centre for Craniofacial and Regenerative Biology, London, United Kingdom; 3King’s College London - Guy’s Campus, Diabetes and Nutritional Sciences Division, London, United Kingdom


A tightly regulated stress system is pivotal for health and the adrenal cortex is a master regulator of the endocrine stress response. The adrenal cortex is characterized by constant cell renewal in part mediated by differentiation and lineage conversion of undifferentiated cell types. To date, the contribution of stem cells to organ plasticity during stress has been implicated but is not fully understood. Recently, we were able to show that a prolonged stress exposure leads to differentiation of non-steroidogenic Nestin-GFP progenitors into specialized cell types in the adrenal cortex of mice. These cells reside in the stem cell niche during homeostasis. The niche in the outermost layer of the adrenal cortex, the capsule and zona glomerulosa, is tightly regulated by signaling pathways including SHH and WNT, which control maintenance and differentiation. However, recent research suggests that YAP/TAZ signaling may further regulate adrenocortical maintenance, since ablation of effector genes leads to degeneration of the organ. Our study explores a functional role for YAP/TAZ downstream signaling in the adrenal cortex during homeostasis and stress. We show that YAP/TAZ targets are normally expressed in different cell types throughout the adrenal cortex including in the stress-responsive Nestin-GFP(+) progenitor cells. We show that during stress, YAP/TAZ targets expressed in the stem cell niche are upregulated. This upregulation is accompanied by downregulation of WNT target genes in the zona Glomerulosa, suggesting differentiation of progenitor cells in this zone. In an in vitro cell differentiation model of adrenocortical progenitors, YAP/TAZ target upregulation accompanied by WNT target downregulation favors adrenocortical differentiation. We further show that YAP/TAZ signaling decreases in HPA-axis inhibiting conditions leading to quiescence of the cells. In summary, this study introduces the YAP/TAZ cascade as putative regulator of the adrenocortical stem cell niche which may be upregulated in stress conditions to mediate differentiation.

Volume 73

European Congress of Endocrinology 2021

Online
22 May 2021 - 26 May 2021

European Society of Endocrinology 

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