TY - JOUR
T1 - Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress
AU - Steenblock, Charlotte
AU - Rubin de Celis, Maria F.
AU - Delgadillo Silva, Luis F.
AU - Pawolski, Verena
AU - Brennand, Ana
AU - Werdermann, Martin
AU - Berger, Ilona
AU - Santambrogio, Alice
AU - Peitzsch, Mirko
AU - Andoniadou, Cynthia L.
AU - Schally, Andrew V.
AU - Bornstein, Stefan R.
N1 - Funding Information:
We thank Uta Lehnert and Linda Friedrich for technical assistance, Doreen Streichert for performing the EM experiments, and Celso Gomez-Sanchez for the CYB11B2 antibodies. This study was supported by the TransCampus initiative between Technische Universität Dresden and King’s College London and by the DFG Grants CRC/Transregio 205/1 “The Adrenal: Central Relay in Health and Disease” (to C.S., C.L.A., and S.R.B.), IRTG2251 (to C.S., C.L.A., and S.R.B.), SFB655 (to S.R.B.), and CRC252 (to S.R.B.).
Funding Information:
ACKNOWLEDGMENTS. We thank Uta Lehnert and Linda Friedrich for technical assistance, Doreen Streichert for performing the EM experiments, and Celso Gomez-Sanchez for the CYB11B2 antibodies. This study was supported by the TransCampus initiative between Technische Universität Dresden and King’s College London and by the DFG Grants CRC/Transregio 205/1 “The Adrenal: Central Relay in Health and Disease” (to C.S., C.L.A., and S.R.B.), IRTG2251 (to C.S., C.L.A., and S.R.B.), SFB655 (to S.R.B.), and CRC252 (to S.R.B.).
Publisher Copyright:
© 2018 National Academy of Sciences. All rights reserved.
PY - 2018/12/18
Y1 - 2018/12/18
N2 - 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.
AB - 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.
KW - Adrenal
KW - Cortex
KW - Progenitors
KW - Stress
KW - Tem cells
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U2 - 10.1073/pnas.1814072115
DO - 10.1073/pnas.1814072115
M3 - Article
C2 - 30514817
AN - SCOPUS:85058686000
VL - 115
SP - 12997
EP - 13002
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 51
ER -