Document Type
Article
Publication Date
11-20-2023
Original Citation
Ruiz-Babot G,
Eceiza A,
Abollo-Jiménez F,
Malyukov M,
Carlone D,
Borges K,
Da Costa A,
Qarin S,
Matsumoto T,
Morizane R,
Skarnes W,
Ludwig B,
Chapple P,
Guasti L,
Storr H,
Bornstein S,
Breault D.
Generation of glucocorticoid-producing cells derived from human pluripotent stem cells. Cell Rep Methods. 2023;3(11):100627.
Keywords
JGM, Humans, Glucocorticoids, Adrenal Insufficiency, Adrenocorticotropic Hormone, Pluripotent Stem Cells, Receptors, Corticotropin
JAX Source
Cell Rep Methods. 2023;3(11):100627.
ISSN
2667-2375
PMID
37924815
DOI
https://doi.org/10.1016/j.crmeth.2023.100627
Grant
This work was supported by grants from IFCAH (to G.R.B. and D.T.B.), the EU-Marie-Cu- rie Fellowship 835533 (to G.R.B.), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) project no. 314061271, TRR 205/1: ‘‘The Adrenal: Central Relay in Health and Disease’’ (to G.R.B. and S.R.B.), the MRC Clinical Training Fellowship Grant Ref: MR/P019897/1 (to A.R.D.C.), and BBSRC (BB/V007246/1) (to L.G.).
Abstract
Adrenal insufficiency is a life-threatening condition resulting from the inability to produce adrenal hormones in a dose- and time-dependent manner. Establishing a cell-based therapy would provide a physiologically responsive approach for the treatment of this condition. We report the generation of large numbers of human-induced steroidogenic cells (hiSCs) from human pluripotent stem cells (hPSCs). Directed differentiation of hPSCs into hiSCs recapitulates the initial stages of human adrenal development. Following expression of steroidogenic factor 1, activation of protein kinase A signaling drives a steroidogenic gene expression profile most comparable to human fetal adrenal cells, and leads to dynamic secretion of steroid hormones, in vitro. Moreover, expression of the adrenocorticotrophic hormone (ACTH) receptor/co-receptor (MC2R/MRAP) results in dose-dependent ACTH responsiveness. This protocol recapitulates adrenal insufficiency resulting from loss-of-function mutations in AAAS, which cause the enigmatic triple A syndrome. Our differentiation protocol generates sufficient numbers of hiSCs for cell-based therapy and offers a platform to study disorders causing adrenal insufficiency.
Comments
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).