Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation.
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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DOI：
10.1126/sciadv.abe4497
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发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Chen A
中科院分区：
文献类型：
--
作者：
Lopez JP;Brivio E;Santambrogio A;De Donno C;Kos A;Peters M;Rost N;Czamara D;Brückl TM;Roeh S;Pöhlmann ML;Engelhardt C;Ressle A;Stoffel R;Tontsch A;Villamizar JM;Reincke M;Riester A;Sbiera S;Fassnacht M;Mayberg HS;Craighead WE;Dunlop BW;Nemeroff CB;Schmidt MV;Binder EB;Theis FJ;Beuschlein F;Andoniadou CL;Chen A
使用单细胞RNA测序的HPA轴解剖揭示了肾上腺ABCB 1作为应激适应的重要参与者。神经内分泌应激反应的慢性激活和失调具有严重的生理和心理后果，包括与代谢和应激相关的精神疾病的发展。我们提供了基线和慢性应激条件下丘脑-垂体-肾上腺轴所有三个组成部分的第一个公正的、细胞类型特异性的分子表征。其中，我们确定了一个以前未报道的Abcb 1b+细胞亚群参与肾上腺的应激适应。我们在小鼠应激模型、库欣综合征患者的肾上腺组织、肾上腺皮质细胞系、外周皮质醇和抑郁症患者的基因分型数据中验证了我们的发现。这个广泛的数据集为研究人员和临床医生提供了宝贵的资源，他们对生物体对压力的神经和内分泌反应以及这些组织之间的相互作用感兴趣。我们的研究结果提出了一种可能性，即调节ABCB 1功能可能对代谢和应激相关精神疾病患者的治疗策略的发展很重要。
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.
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影响因子：
4.8
作者：
Cheung, Leonard Y. M.;George, Akima S.;Camper, Sally A.
通讯作者：
Camper, Sally A.
DOI：
10.1196/annals.1314.048
发表时间：
2004-01-01
期刊：
BIOBEHAVIORAL STRESS RESPONSE: PROTECTIVE AND DAMAGING EFFECTS
影响因子：
--
作者：
Karssen, AM;Meijer, OC;De Kloet, ER
通讯作者：
De Kloet, ER
影响因子：
3
作者：
Herman JP
通讯作者：
Herman JP
影响因子：
2.2
作者：
Lichtenauer, U. D.;Shapiro, I.;Beuschlein, F.
通讯作者：
Beuschlein, F.
影响因子：
2.1
作者：
Johnson, W. Evan;Li, Cheng;Rabinovic, Ariel
通讯作者：
Rabinovic, Ariel