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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-12, Vol.115 (51), p.12997-13002
Main Authors: Steenblock, Charlotte, de Celis, Maria F. Rubin, Silva, Luis F. Delgadillo, Pawolski, Verena, Brennand, Ana, Werdermann, Martin, Berger, Ilona, Santambrogio, Alice, Peitzsch, Mirko, Andoniadou, Cynthia L., Schally, Andrew V., Bornstein, Stefan R.
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Adrenal cortex
Adrenal Cortex - cytology
Adrenal Cortex - physiology
Adrenal glands
Adrenocorticotropic hormone
Adrenocorticotropic Hormone - metabolism
Angiotensin
Angiotensin II
Animals
Biological Sciences
Cell Differentiation
Cells (biology)
Cells, Cultured
Glucocorticoids
Gonadotropin-releasing hormone
Homeostasis
Human behavior
Luteinizing hormone
Medulla oblongata
Mice
Nestin
Progenitor cells
Stem cells
Stem Cells - cytology
Stem Cells - physiology
Stress
Stress, Physiological
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1814072115