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

Lopez, Juan Pablo; Brivio, Elena; Santambrogio, Alice; De Donno, Carlo; Kos, Aron; Peters, Miriam; Rost, Nicolas; Czamara, Darina; Brueckl, Tanja; Roeh, Simone; Poehlmann, Max L.; Engelhardt, Clara; Ressle, Andrea; Stoffel, Rainer; Tontsch, Alina; Villamizar, Javier M.; Reincke, Martin; Riester, Anna; Sbiera, Silviu; Fassnacht, Martin; Mayberg, Helen S.; Craighead, W. Edward; Dunlop, Boadie W.; Nemeroff, Charles B.; Schmidt, Mathias V.; Binder, Elisabeth B.; Theis, Fabian J.; Beuschlein, Felix; Andoniadou, Cynthia L.; Chen, Alon

doi:10.1126/sciadv.abe4497

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

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Lopez, Juan Pablo
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Brivio, Elena
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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De Donno, Carlo
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Kos, Aron
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Rost, Nicolas
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80291

Czamara, Darina
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80280

Brueckl, Tanja
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Roeh, Simone
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Poehlmann, Max L.
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons207257

Engelhardt, Clara
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons136556

Ressle, Andrea
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons200349

Stoffel, Rainer
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80555

Tontsch, Alina
Max Planck Institute of Psychiatry, Max Planck Society;

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Schmidt, Mathias V.
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

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Binder, Elisabeth B.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons129892

Chen, Alon
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Lopez, J. P., Brivio, E., Santambrogio, A., De Donno, C., Kos, A., Peters, M., et al. (2021). Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation. SCIENCE ADVANCES, 7(5): eabe4497. doi:10.1126/sciadv.abe4497.

Cite as: https://hdl.handle.net/21.11116/0000-0008-E188-0

Abstract

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 hypothalamicpituitary-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.