In vitro differentiation of mouse pluripotent stem cells into corticosteroid-producing adrenocortical cells.
Stem Cell Reports
; 19(9): 1289-1303, 2024 Sep 10.
Article
in En
| MEDLINE
| ID: mdl-39178848
ABSTRACT
Directed differentiation of pluripotent stem cells into specialized cell types represents an invaluable tool for a wide range of applications. Here, we have exploited single-cell transcriptomic data to develop a stepwise in vitro differentiation system from mouse embryonic stem cells into adrenocortical cells. We show that during development, the adrenal primordium is embedded in an extracellular matrix containing tenascin and fibronectin. Culturing cells on fibronectin during differentiation increased the expression of the steroidogenic marker NR5A1. Furthermore, 3D cultures in the presence of protein kinase A (PKA)-pathway activators led to the formation of aggregates composed of different cell types expressing adrenal progenitor or steroidogenic markers, including the adrenocortical-specific enzyme CYP21A1. Importantly, in-vitro-differentiated cells responded to adrenocorticotropic hormone (ACTH) and angiotensin II with the production of glucocorticoids and mineralocorticoids, respectively, thus confirming the specificity of differentiation toward the adrenal lineage.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Differentiation
/
Pluripotent Stem Cells
Limits:
Animals
Language:
En
Journal:
Stem Cell Reports
Year:
2024
Document type:
Article
Affiliation country:
Germany
Country of publication:
United States