PuSH - Publication Server of Helmholtz Zentrum München: Cell-type-specific impact of glucocorticoid receptor activation on the developing brain: A cerebral organoid study.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Cruceanu, C.* ; Dony, L. ; Krontira, A.C.* ; Fischer, D.S. ; Roeh, S.* ; Di Giaimo, R.* ; Kyrousi, C.* ; Kaspar, L.* ; Knauer-Arloth, J. ; Czamara, D.* ; Martinelli, S.* ; Wehner, S.* ; Breen, M.S.* ; Koedel, M.* ; Sauer, S.* ; Sportelli, V.* ; Rex-Haffner, M.* ; Cappello, S. ; Theis, F.J. ; Binder, E.B.*

Cell-type-specific impact of glucocorticoid receptor activation on the developing brain: A cerebral organoid study.

Am. J. Psychiatry 179, 375-387 (2021)

Postprint

DOI

PMC

	Open Access Green

Abstract
Metrics
Extra information

OBJECTIVE: A fine-tuned balance of glucocorticoid receptor (GR) activation is essential for organ formation, with disturbances influencing many health outcomes. In utero, glucocorticoids have been linked to brain-related negative outcomes, with unclear underlying mechanisms, especially regarding cell-type-specific effects. An in vitro model of fetal human brain development, induced human pluripotent stem cell (hiPSC)-derived cerebral organoids, was used to test whether cerebral organoids are suitable for studying the impact of prenatal glucocorticoid exposure on the developing brain. METHODS: The GR was activated with the synthetic glucocorticoid dexamethasone, and the effects were mapped using single-cell transcriptomics across development. RESULTS: The GR was expressed in all cell types, with increasing expression levels through development. Not only did its activation elicit translocation to the nucleus and the expected effects on known GR-regulated pathways, but also neurons and progenitor cells showed targeted regulation of differentiation- and maturation-related transcripts. Uniquely in neurons, differentially expressed transcripts were significantly enriched for genes associated with behavior-related phenotypes and disorders. This human neuronal glucocorticoid response profile was validated across organoids from three independent hiPSC lines reprogrammed from different source tissues from both male and female donors. CONCLUSIONS: These findings suggest that excessive glucocorticoid exposure could interfere with neuronal maturation in utero, leading to increased disease susceptibility through neurodevelopmental processes at the interface of genetic susceptibility and environmental exposure. Cerebral organoids are a valuable translational resource for exploring the effects of glucocorticoids on early human brain development.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Biology ; Brain ; Child/adolescent Psychiatry ; Development ; Glucocorticoid Receptor ; Neurodevelopmental Disorders ; Pre/peri/postnatal Issues ; Stress ; Translational Research; Gene-expression; Antenatal Corticosteroids; Preterm Birth; Stress; Generation; Depression; Management; Disorders; Landscape; Exposure

ISSN (print) / ISBN 0002-953X

e-ISSN 1535-7228

Journal American Journal of Psychiatry, The

Quellenangaben Volume: 179, Issue: 5, Pages: 375-387

Publisher American Psychiatric Association

Publishing Place 800 Maine Ave Sw, Suite 900, Washington, Dc 20024 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)