The adrenal cortex is the major site of production of steroid hormones, which are essential for life. The normal development and homeostatic renewal of the adrenal cortex depend on capsular stem cells and cortical progenitor cells. These cell populations are highly plastic and support adaptation to physiological demands, injury and disease, linking steroid production and adrenal (organ) homeostasis with systemic endocrine cues and organismal homeostasis. This Review integrates findings from the past decade, outlining the mechanisms that govern the establishment and maintenance of the adrenal stem cell niche under different physiological and pathological conditions. The sophisticated regulation of the stem cell niche by gene regulatory networks, coordinated through paracrine and endocrine signalling, is highlighted in a context-dependent and sex-specific manner. We discuss how dysregulation of this intricate regulatory network is implicated in a wide range of adrenal diseases, and how emerging knowledge from adrenal stem cell research is inspiring the future development of gene-based and cell-based therapeutic strategies.
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