Modeling human prenatal adrenocortical functional zonation dynamics from pluripotent stem cells - PubMed
4 days ago
- #steroidogenesis
- #stem cells
- #adrenal organoids
- Researchers developed a human pluripotent stem cell-derived adrenal organoid system to model prenatal adrenocortical functional zonation dynamics.
- The system recapitulates the concentric zonal architecture of the adrenal cortex, including definitive zone (DZ) progenitors specified by RSPO3/WNT signaling.
- DZ progenitors differentiate into cortisol-producing transitional zones and androgen-producing fetal zones under the influence of RSPO3 and ACTH.
- Loss of NR0B1 impairs DZ specification, leading to direct adrenal primordium-to-fetal zone conversion, mirroring X-linked adrenal hypoplasia congenita.
- Encapsulating DZ cells with capsule cells in vivo reconstitutes zonation, forming ACTH-responsive tissue that produces cortisol and androgens.
- This organoid platform provides insights into human adrenal development and potential regenerative therapies for adrenal diseases.