ECE2024 Eposter Presentations Adrenal and Cardiovascular Endocrinology (155 abstracts)
In vitro differentiation of mouse pluripotent stem cells into glucocorticoid-producing adrenocortical cells
Ioannis Oikonomakos 1,2 , Yasmine Neirijnck 2 , Melina Tedesco 2 , Fariba Jian Motamedi 2 , Serge Nef 3 , Stefan Bornstein 1,4 , Charlotte Steenblock 1 & Andreas Schedl 2
1University Hospital Carl Gustav Carus Dresden, Department of Internal Medicine III, Dresden, Germany; 2Institute Of Biology Valrose - iBV, Nice, France; 3University of Geneva, Department of Genetic Medicine and Development, Geneva, Switzerland; 4King’s College London, Faculty of Life Sciences & Medicine, United Kingdom
The adrenal cortex, a pivotal endocrine regulator governing body homeostasis, metabolism, and stress response through steroid hormone synthesis, presents formidable challenges for effective replacement in disorders like adrenal insufficiency and congenital adrenal hyperplasia. The limitations of current hormone replacement strategies stem from the intricate dynamics of hormonal release. This study harnesses insights derived from the analysis of a recently published single-cell atlas of the mouse to establish a robust differentiation protocol for mouse embryonic stem cells (mESCs) into adrenocortical-like cells. Key findings reveal the expression of critical adrenal progenitor markers (Gata4, Wt1, Nr5a1, Mc2r) during the differentiation of the cells. Furthermore, we identified Tenascin and Fibronectin as pivotal extracellular matrix proteins influencing adrenocortical development. Notably, culturing cells on Fibronectin during differentiation enhanced the expression of NR5A1, the master regulator of steroidogenesis. In parrarel, we saw that by employing 3D aggregates in microwell culture induced the expression of essential steroidogenic enzymes, including the adrenocortical-specific enzymes Cyp21a1 and Cyp11b1. Importantly, these aggregates demonstrated the production and secretion of glucocorticoids, validating specific differentiation towards the adrenocortical lineage. Crucially, no gonad-specific steroids were detected in the medium, affirming the specificity of the differentiation protocol. This study provides insights into the extracellular matrix supporting adrenocortical development and outlines a step-wise protocol for differentiating mouse ES cells into glucocorticoid-producing adrenocortical cells. The directed differentiation of pluripotent stem cells offers a promising avenue for innovative cell replacement therapies, holding potential for a lasting cure in patients with adrenal disorders.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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