Adrenal stem cells under homeostatic and stress conditions

Principal Investigators

Scientific Staff

Alice Santambrogio – PhD Student
Ilona Berger – PhD Student

Project Description

Project A06 deals with the adrenal response to stress. It aims to characterize stem/progenitors with regenerative capacity of the hypothalamic–pituitary–adrenal (HPA) axis and the functional role of signal transduction mechanisms in these processes. Thus, they focus on the regeneration and stress adaptation mechanisms in the HPA axis and the potential involvement of progenitors in maladaptation, which will be of clinical importance. Furthermore, they work on the differentiation of different stem cells into steroidogenic cells in order to restore adrenal insufficiency.

Aims

(I) Utilise in vitro differentiated murine ES cells to restore adrenal insufficiency.

(II) Evaluate the behaviour of HPA axis progenitors following perturbation of the HPA axis in mice and humans.

(III) Characterise the molecular dynamics involved in the pathogenesis of stress-associated disorders utilising omics approaches.

PhD/MD-Thesis

Characterization of Sox2 positive stem cells in the adrenal and their role in stress: Alice Santambrogio, Sep. 2017-Aug. 2021.

Characterisation of stem cells of the hypothalamic-pituitary-adrenal axis during stress: Ilona Berger, Feb. 2018-Jun. 2021.

Characterisation of Adrenal Stem Cells in Metabolic Disease: Laura D. Scriba, Oct. 2018-Sep. 2019.

The influence of obesity and diabetes on the function of adult stem cells of the hypothalamic-pituitary-adrenal axis: Martin Werdermann, Oct. 2017-Sep. 2018.

Publications

Lyraki R, Schedl A. The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease. Int J Mol Sci. 2021;22(9):4889.

Lyraki R, Schedl A. Adrenal cortex renewal in health and disease. Nat Rev Endocrinol. 2021;17(7):421-434.

Oikonomakos I, Weerasinghe Arachchige LC, Schedl A. Developmental mechanisms of adrenal cortex formation and their links with adult progenitor populations. Mol Cell Endocrinol. 2021;524:111172.

Steenblock C, Richter S, Berger I, Barovic M, Schmid J, Schubert U, Jarzebska N, von Mässenhausen A, Linkermann A, Schürmann A, Pablik J, Dienemann T, Evert K, Rodionov RN, Semenova NY, Zinserling VA, Gainetdinov RR, Baretton G, Lindemann D, Solimena M, Ludwig B,Bornstein SR. Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun. 2021;12(1):3534.

Bechmann N, Watts D, Steenblock C, Wallace PW, Schürmann A, Bornstein SR, Wielockx B, Eisenhofer G, Peitzsch M. Adrenal Hormone Interactions and Metabolism: A Single Sample Multi-Omics Approach. Horm Metab Res. 2021;53(5):326-334.

Bechmann N, Berger I, Bornstein SR, Steenblock C. Adrenal medulla development and medullary-cortical interactions. Mol Cell Endocrinol. 2021;528:111258.

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. Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation. Sci Adv. 2021;7(5):eabe4497.

Russell JP, Lim X, Santambrogio A, Yianni V, Kemkem Y, Wang B, Fish M, Haston S, Grabek A, Hallang S, Lodge EJ, Patist AL, Schedl A, Mollard P, Nusse R, Andoniadou CL. Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells. Elife. 2021;10:e59142.

Werdermann M, Berger I, Scriba LD, Santambrogio A, Schlinkert P, Brendel H, Morawietz H, Schedl A, Peitzsch M, King AJF, Andoniadou CL, Bornstein SR, Steenblock C. Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state. Mol Metab. Mol Metab. 2021;43:101112.

Bornstein SR, Malyukov M, Heller C, Ziegler CG, Ruiz-Babot G, Schedl A, Ludwig B, Steenblock C.New horizons: novel adrenal regenerative therapies. J Clin Endocrinol Metab. 2020;105(9):3103-7.

Grabek A, Dolfi B, Klein B, Jian-Motamedi F, Chaboissier MC, Schedl A.The adult adrenal cortex undergoes rapid tissue renewal in a sex-specific manner. Cell Stem Cell. 2019;25(2):290-296.e2.

Bornstein SR, Berger I, Steenblock C. Are Nestin-positive cells responsive to stress? Stress. 2020:1-5. doi: 10.1080/10253890.2020.1766441.

Steenblock C, Todorov V, Kanczkowski W, Eisenhofer G, Schedl A, Wong ML, Licinio J, Bauer M, Young AH, Gainetdinov RR, Bornstein SR. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Neuroendocrine Stress Axis. Mol Psychiatry. 2020;25(8):1611-1617.

ScribaLD, Bornstein SR, Santambrogio A, Mueller G, Huebner A, Hauer J, Schedl A, Wielockx B, Eisenhofer G, Andoniadou CL, Steenblock C. Cancer stem cells in pheochromocytoma and paraganglioma. Front Endocrinol (Lausanne). 2020, 11:79.

Bornstein SR, Berger I, Scriba L, Santambrogio A, Steenblock C. Adrenal cortex–medulla interactions in adaptation to stress and disease. Curr Opin Endocrin Metabol Res. 2019, 8:9-14.

Xekouki P, Lodge EJ, Matschke J,Santambrogio A, Apps JR, Sharif A, Jacques TS, Aylwin S, Prevot V, Li R, Flitsch J, Bornstein SR, Theodoropoulou M, Andoniadou CL. Non-secreting pituitary tumours characterised by enhanced expression of YAP/TAZ. Endocr Relat Cancer. 2019;26(1):215-225.

Berger I, Werdermann M, Bornstein SR, Steenblock C. The adrenal gland in stress – Adaptation on a cellular level. J Steroid Biochem Mol Biol. 2019;190:198-206.

Bornstein SR, Steenblock C, Chrousos GP, Schally AV, Beuschlein F, Kline G, Krone NP, Licinio J, Wong ML, Ullmann E, Ruiz-Babot G, Boehm BO, Behrens A, Brennand A, Santambrogio A,

Berger I, Werdermann M, Sancho R, Linkermann A, Lenders JW, Eisenhofer G, Andoniadou CL. Stress-inducible-stem cells: a new view on endocrine, metabolic and mental disease? Mol Psychiatry. 2019, 24:2-9.

Lodge EJ,Santambrogio A, Russell JP, Xekouki P, Jacques TS, Johnson RL, Thavaraj S, Bornstein SR, Andoniadou CL. Homeostatic and tumourigenic activity of SOX2+ pituitary stem cells is controlled by the LATS/YAP/TAZ cascade. Elife. 2019;8:e43996.

Steenblock C, Rubin de Celis MF, Delgadillo Silva LF, Pawolski V, Brennand A, Werdermann M, Berger I, Santambrogio A, Peitzsch M, Andoniadou CL, Schally AV, Bornstein SR. Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress. Proc Natl Acad Sci U S A. 2018, 115:12997-13002.

Balyura M, Gelfgat E, Steenblock C, Androutsellis-Theotokis A, Ruiz-Babot G, Guasti L, Werdermann M, Ludwig B, Bornstein T, Schally AV, Brennand A, Bornstein SR. Expression of progenitor markers is associated with the functionality of a bioartificial adrenal cortex. PLoS One. 2018;13(3):e0194643.

Langton K, Gruber M, Masjkur J, Steenblock C, Peitzsch M, Meinel J, Lenders J, Bornstein S, Eisenhofer G. Hypertensive crisis in pregnancy due to a metamorphosing pheochromocytoma with postdelivery Cushing’s syndrome. Gynecol Endocrinol. 2018;34(1):20-24.

Steenblock C, Rubin de Celis MF, Androutsellis-Theotokis A, Sue M, Delgadillo Silva LF, Eisenhofer G, Andoniadou CL, Bornstein SR: Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation? Mol Cell Endocrinol 2017, 441:156-163.