Adrenal

The adrenal cortex is a central endocrine organ responsible for steroid hormone production, regulating essential physiological processes including stress adaptation, immune function, sexual maturation, and electrolyte balance. Despite its critical role in human health, the molecular and cellular mechanisms governing human adrenal cortex development and steroid biosynthesis remain poorly understood, largely due to the lack of physiologically relevant human model systems.

We have established the first human induced pluripotent stem cell (iPSC)-derived prenatal adrenal organoid platform that faithfully recapitulates key features of normal adrenocortical development and functional steroidogenesis. This system provides a powerful and experimentally tractable model to interrogate human stem cell fate decisions, lineage specification, and tissue self-organization within the adrenal lineage.

Leveraging this platform, we aim to define the cellular hierarchies, signaling pathways, and gene regulatory networks that orchestrate human adrenocortical development and steroid hormone production. Beyond modeling development, this organoid system serves as a transformative framework to study stem cell dynamics in endocrine tissue formation and regeneration. Ultimately, our work seeks to illuminate the mechanisms underlying disorders such as primary adrenal insufficiency and adrenal androgen excess, while laying the groundwork for future regenerative strategies to restore adrenal function.

Human pluripotent stem cell–derived adrenocortical organoids transplanted under the kidney capsule of NCG mice reestablish zonal organization. NOV⁺ progenitors (blue) differentiate centripetally into CYP17A1⁺ steroidogenic zones (green), with all adrenocortical cells marked by NR5A1 (red). This system recapitulates human adrenal zonation and produces ACTH-responsive, cortisol-secreting tissue in vivo.