Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation
| Autor: | Felix Beuschlein, Charles B. Nemeroff, Max L. Pöhlmann, Fabian J. Theis, Mathias V. Schmidt, Anna Riester, W. Edward Craighead, Martin Fassnacht, Rainer Stoffel, Cynthia L. Andoniadou, Tanja Brückl, Clara Engelhardt, Elena Brivio, Carlo De Donno, Helen S. Mayberg, Nicolas Rost, Martin Reincke, Alina Tontsch, Miriam Peters, Javier M. Villamizar, Darina Czamara, Alon Chen, Aron Kos, Andrea Ressle, Boadie W. Dunlop, Juan Pablo Lopez, Alice Santambrogio, Elisabeth B. Binder, Simone Roeh, Silviu Sbiera |
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| Rok vydání: | 2021 |
| Předmět: |
endocrine system
Cell Regulator Diseases and Disorders Bioinformatics 03 medical and health sciences 0302 clinical medicine medicine Endocrine system Chronic stress Genotyping Research Articles 030304 developmental biology 0303 health sciences Multidisciplinary Adrenal gland business.industry SciAdv r-articles Stress adaptation ddc medicine.anatomical_structure business human activities 030217 neurology & neurosurgery Function (biology) Research Article Neuroscience |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.abe4497 |
| Popis: | Dissection of the HPA axis using single-cell RNA sequencing uncovers adrenal ABCB1 as an important player of stress adaptation. 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. |
| Databáze: | OpenAIRE |
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