Sex shapes cell-type-specific transcriptional signatures of stress exposure in the mouse hypothalamus
Elena Brivio,
Aron Kos,
Alessandro Francesco Ulivi,
Stoyo Karamihalev,
Andrea Ressle,
Rainer Stoffel,
Dana Hirsch,
Gil Stelzer,
Mathias V. Schmidt,
Juan Pablo Lopez,
Alon Chen
Affiliations
Elena Brivio
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany; International Max Planck Research School for Translational Psychiatry (IMPRS-TP), 80804 Munich, Germany; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Brain Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
Aron Kos
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany
Alessandro Francesco Ulivi
Department of Cellular Neuroscience, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany
Stoyo Karamihalev
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany; International Max Planck Research School for Translational Psychiatry (IMPRS-TP), 80804 Munich, Germany
Andrea Ressle
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany
Rainer Stoffel
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany
Dana Hirsch
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel
Gil Stelzer
Bioinformatics Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel
Mathias V. Schmidt
Research Group Neurobiology of Stress Resilience, Max Planck Institute of Psychiatry, 80804 Munich, Germany
Juan Pablo Lopez
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany; Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden; Corresponding author
Alon Chen
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Brain Sciences, Weizmann Institute of Science, Rehovot 76100, Israel; Corresponding author
Summary: 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 signatures 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 signatures 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 individual 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.
