Sex shapes cell-type-specific transcriptional signatures of stress exposure in 
the mouse hypothalamus

Brivio, Elena; Kos, Aron; Ulivi, Alessandro Francesco; Karamihalev, Stoyo; Reßle, Andrea; Stoffel, Rainer; Hirsch, Dana; Stelzer, Gil; Schmidt, Mathias V.; Lopez, Juan Pablo; Chen, Alon

doi:10.1016/j.celrep.2023.112874

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Sex shapes cell-type-specific transcriptional signatures of stress exposure in the mouse hypothalamus

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Brivio, Elena
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Kos, Aron
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Karamihalev, Stoyo
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Reßle, Andrea
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Stoffel, Rainer
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Schmidt, Mathias V.
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

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Lopez, Juan Pablo
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Chen, Alon
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Brivio, E., Kos, A., Ulivi, A. F., Karamihalev, S., Reßle, A., Stoffel, R., et al. (2023). Sex shapes cell-type-specific transcriptional signatures of stress exposure in the mouse hypothalamus. CELL REPORTS, 42(8): 112874. doi:10.1016/j.celrep.2023.112874.

Cite as: https://hdl.handle.net/21.11116/0000-000D-A6B3-D

Abstract

Stress-related psychiatric disorders and the stress system show prominent differences between males and females, as well as strongly divergent transcriptional changes. Despite several proposed mechanisms, we still lack the understanding of the molecular processes at play. Here, we explore the contribution of cell types to transcriptional sex dimorphism using single-cell RNA sequencing. We identify cell-type-specific signa-tures of acute restraint stress in the paraventricular nucleus of the hypothalamus, a central hub of the stress response, in male and female mice. Further, we show that a history of chronic mild stress alters these signa-tures in a sex-specific way, and we identify oligodendrocytes as a major target for these sex-specific effects. This dataset, which we provide as an online interactive app, offers the transcriptomes of thousands of indi-vidual cells as a molecular resource for an in-depth dissection of the interplay between cell types and sex on the mechanisms of the stress response.