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Plate IV.332 · Publications

Cell-type specific impact of glucocorticoid receptor activation on the developing brain

Preprint in bioRxiv, 9 January 2020.

PreprintOpen accessBrain, Neurons, Reprogramming

  1. Cristiana Cruceanu
  2. Leander Dony
  3. Anthi C. Krontira
  4. David S. Fischer
  5. Simone Roeh
  6. Rossella Di Giaimo
  7. Christina Kyrousi
  8. Janine Arloth
  9. Darina Czamara
  10. Silvia Martinelli
  11. Stefanie Wehner
  12. Michael S. Breen
  13. Maik Koedel
  14. Susann Sauer
  15. Monika Rex-Haffner
  16. Silvia Cappello
  17. Fabian J. Theis
  18. Elisabeth B. Binder

Abstract

A fine-tuned balance of glucocorticoid receptor (GR) activation is essential for organ formation, with disturbances influencing health outcomes. Excess GR-activation in utero has been linked to brain-related negative outcomes, with unclear underlying mechanisms, especially regarding cell-type specific effects. To address this, we used an in vitro model of fetal human brain, induced pluripotent-stem-cell-derived cerebral organoids, and mapped GR-activation effects using single-cell transcriptomics across development. Interestingly, neurons showed targeted regulation of differentiation- and maturation-related transcripts, suggesting a delay of these processes upon GR-activation. Uniquely in neurons, differentially-expressed transcripts were significantly enriched for genes associated with behavior-related phenotypes and disorders. This suggests that aberrant GR-activation could impact proper neuronal maturation, leading to increased disease susceptibility, through neurodevelopmental processes at the interface of genetic susceptibility and environmental exposure.

Cite

@misc{cruceanu2020cell,
  title = {{Cell-type specific impact of glucocorticoid receptor activation on the developing brain}},
  author = {Cruceanu, Cristiana and Dony, Leander and Krontira, Anthi C. and Fischer, David S. and Roeh, Simone and Di Giaimo, Rossella and Kyrousi, Christina and Arloth, Janine and Czamara, Darina and Martinelli, Silvia and Wehner, Stefanie and Breen, Michael S. and Koedel, Maik and Sauer, Susann and Rex-Haffner, Monika and Cappello, Silvia and Theis, Fabian J. and Binder, Elisabeth B.},
  howpublished = {bioRxiv},
  publisher = {openRxiv},
  year = {2020},
  month = jan,
  doi = {10.1101/2020.01.09.897868},
  url = {https://doi.org/10.1101/2020.01.09.897868},
  note = {Preprint}
}
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