In vitro differentiation of mouse pluripotent stem cells into corticosteroid-producing adrenocortical cells

• DOI: 10.1016/j.stemcr.2024.07.010
• Publication Date: 2024-08-23T07:39:59Z
• Authors: Ioannis Oikonomakos; Melina Tedesco; Fariba Jian Motamedi; Mirko Peitzsch; Serge Nef; Stefan R. Bornstein; Andreas Schedl; Charlotte Steenblock; Yasmine Neirijnck
• Keywords: Lineage markers

Directed differentiation of pluripotent stem cells into specialized cell types represents an invaluable tool for a wide range applications. Here, we have exploited single-cell transcriptomic data to develop stepwise in vitro system from mouse embryonic adrenocortical cells. We show that during development, the adrenal primordium is embedded extracellular matrix containing tenascin and fibronectin. Culturing on fibronectin increased expression steroidogenic marker NR5A1. Furthermore, 3D cultures presence protein kinase A (PKA)-pathway activators led formation aggregates composed different expressing progenitor or markers, including adrenocortical-specific enzyme CYP21A1. Importantly, in-vitro-differentiated responded adrenocorticotropic hormone (ACTH) angiotensin II with production glucocorticoids mineralocorticoids, respectively, thus confirming specificity toward lineage.