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

Stress-related psychiatric disorders and the stress system show prominent differences between men and women. These sex differences are detectable at the transcriptional level but we lack cell-type specific information. Here, using single-cell transcriptomics, 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 acute stress signatures in a sex-specific way. Using this dataset, we identified oligodendrocytes as a major target for sex-specific effects of stress. This dataset provides the first molecular resource for an in-depth dissection of the interplay between cell types and sex on the mechanisms of the stress response, offering the transcriptomes of thousands of individual cells. Single-cell RNA-sequencing of male and female mice without (controls) or after stress exposure (acute restraint stress (ARS) or acute restraint stress after chronic mild stress (CMS ARS))