Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress

Charlotte Steenblock, Maria F. Rubin de Celis, Luis F. Delgadillo Silva, Verena Pawolski, A. Brennand, M Werdermann, I Berger, Alice Santambrogio, Mirko Peitzsch, Cynthia Andoniadou, Andrew V Schally, Stefan Bornstein

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The adrenal gland is a master regulator of the human body during response to stress. This organ shows constant replacement of senescent cells by newly differentiated cells. A high degree of plasticity is critical to sustain homeostasis under different physiological demands. This is achieved in part through proliferation and differentiation of adult adrenal progenitors. Here, we report the isolation and characterization of a Nestin+ population of adrenocortical progenitors located under the adrenal capsule and scattered throughout the cortex. These cells are interconnected with progenitors in the medulla. In vivo lineage tracing revealed that, under basal conditions, this population is noncommitted and slowly migrates centripetally. Under stress, this migration is greatly enhanced, and the cells differentiate into steroidogenic cells. Nestin+ cells cultured in vitro also show multipotency, as they differentiate into mineralocorticoid and glucocorticoid-producing cells, which can be further influenced by the exposure to Angiotensin II, adrenocorticotropic hormone, and the agonist of luteinizing hormone-releasing hormone, triptorelin. Taken together, Nestin+ cells in the adult adrenal cortex exhibit the features of adrenocortical progenitor cells. Our study provides evidence for a role of Nestin+ cells in organ homeostasis and emphasizes their role under stress. This cell population might be a potential source of cell replacement for the treatment of adrenal insufficiency.
Original languageEnglish
Pages (from-to)12997-13002
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
Early online date4 Dec 2018
Publication statusPublished - 18 Dec 2018


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