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

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

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

Juan Pablo Lopez, Elena Brivio, Alice Santambrogio, Carlo De Donno, Aron Kos, Miriam Peters, Nicolas Rost, Darina Czamara, Tanja M Brückl, Simone Roeh, …

Science advances, Vol.7(5)

2021-01

DOI: https://doi.org/10.1126/sciadv.abe4497

PMID: 33571131

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 hypothalamic-pituitary-adrenal axis, under baseline and chronic stress conditions. Among others, we identified a previously unreported subpopulation of 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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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.5 Neuroscience; 1.5.420 Cortisol
Web Of Science research areas: Endocrinology & Metabolism
ESI research areas: Biology & Biochemistry

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Title: Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation
Creators: Juan Pablo Lopez - The Max Planck Society-Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics, Rehovot 76100, Israel and Munich, Bavaria 80804, Germany
Elena Brivio - International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Bavaria 80804, Germany
Alice Santambrogio - Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony 01307, Germany
Carlo De Donno - Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria 85764, Germany
Aron Kos - The Max Planck Society-Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics, Rehovot 76100, Israel and Munich, Bavaria 80804, Germany
Miriam Peters - Department for Endocrinology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Bavaria 80336, Germany
Nicolas Rost - Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Darina Czamara - Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Tanja M Brückl - Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Simone Roeh - Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Max L Pöhlmann - Research Group Neurobiology of Stress Resilience, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Clara Engelhardt - Research Group Neurobiology of Stress Resilience, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Andrea Ressle - Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Rainer Stoffel - Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Alina Tontsch - Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Javier M Villamizar - Department for Endocrinology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Bavaria 80336, Germany
Martin Reincke - Department for Endocrinology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Bavaria 80336, Germany
Anna Riester - Department for Endocrinology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Bavaria 80336, Germany
Silviu Sbiera - Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Bavaria 97080, Germany
Martin Fassnacht - Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Bavaria 97080, Germany
Helen S Mayberg - Departments of Neurology and Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
W Edward Craighead - Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA
Boadie W Dunlop - Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA
Charles B Nemeroff - Department of Psychiatry, University of Texas at Austin Dell Medical School, Austin, TX 78738, USA
Mathias V Schmidt - Research Group Neurobiology of Stress Resilience, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Elisabeth B Binder - Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Fabian J Theis - Department of Mathematics, Technische Universität München, Munich, Bavaria 85748, Germany
Felix Beuschlein - Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zurich 8091, Switzerland
Cynthia L Andoniadou - Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony 01307, Germany
Alon Chen - Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Publication Details: Science advances, Vol.7(5)
Grant note: MR/T012153/1 / Medical Research Council
Academic Unit: UMMG Dept of Psychiatry & Behavioral Sciences
Language: English
Resource Type: Journal article
PMID: 33571131
Record Identifier: 991031615280802976