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Lopez, J.P.* ; Brivio, E.* ; Santambrogio, A.* ; De Donno, C. ; Kos, A.* ; Peters, M.* ; Rost, N.* ; Czamara, D.* ; Brückl, T.M.* ; Roeh, S.* ; Pöhlmann, M.L.* ; Engelhardt, C.* ; Ressle, A.* ; Stoffel, R.* ; Tontsch, A.* ; Villamizar, J.M.* ; Reincke, M.* ; Riester, A.* ; Sbiera, S.* ; Fassnacht, M.* ; Mayberg, H.S.* ; Craighead, W.E.* ; Dunlop, B.W.* ; Nemeroff, C.B.* ; Schmidt, M.V.* ; Binder, E.B.* ; Theis, F.J. ; Beuschlein, F.* ; Andoniadou, C.L.* ; Chen, A.*

Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation.

Sci. Adv. 7:eabe4497 (2021)

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Chronic activation and dysregulation of the neuroendocrine stress response have severe physiological and psychological consequences, including the development of metabolic and stress-related psychiatric disorders. We provide the first unbiased, cell type-specific, molecular characterization of all three components of the hypothalamic-pituitary- adrenal axis, under baseline and chronic stress conditions. Among others, we identified a previously unreported subpopulation of Abcb1b+ cells involved in stress adaptation in the adrenal gland. We validated our findings in a mouse stress model, adrenal tissues from patients with Cushing's syndrome, adrenocortical cell lines, and peripheral cortisol and genotyping data from depressed patients. This extensive dataset provides a valuable resource for researchers and clinicians interested in the organism's nervous and endocrine responses to stress and the interplay between these tissues. Our findings raise the possibility that modulating ABCB1 function may be important in the development of treatment strategies for patients suffering from metabolic and stress-related psychiatric disorders.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

ISSN (print) / ISBN 2375-2548

e-ISSN 2375-2548

Journal Science Advances

Quellenangaben Volume: 7, Issue: 5, Article Number: eabe4497

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place Washington, DC [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants Adelis Foundation
U.S. NIH
NIH
Swiss National Science Foundation
Else Kroner-Fresenius Stiftung
Lister Institute of Preventive Medicine (Lister Institute Research Prize)
Medical Research Council
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)
Canadian Biomarker Integration Network in Depression (CAN-BIND)
Alexander von Humboldt Foundation
BMBF
Perlman Family Foundation
Bruno and Simone Licht
Ruhman Family Laboratory for Research in the Neurobiology of Stress
I-CORE Program of the Planning and Budgeting Committee
Federal Ministry of Education and Research
ERANET Program - Chief Scientist Office of the Israeli Ministry of Health
Israel Science Foundation
FP7 Grant from the European Research Council
Chan Zuckerberg Initiative DAF (advised fund of Silicon Valley Community Foundation)
Helmholtz Association
European Molecular Biology Organization