# Single-cell characterization of the adult male hippocampus suggests a prominent, and cell-type specific, role for Nrgn and Sgk1 in response to a social stressor

## TL;DR

This study uses single-cell RNA sequencing to uncover how different cell types in the mouse hippocampus respond to stress, highlighting the roles of Nrgn and Sgk1.

## Contribution

The study identifies cell-type specific molecular signatures and key regulators of stress response in the hippocampus using comprehensive single-cell RNA sequencing.

## Key findings

- Nrgn and SgK1 are key regulators in stress-responsive cell types like neurons and astrocytes.
- GR or MR deletion in specific neurons leads to distinct transcriptional changes after stress.
- The study reveals previously unknown molecular signatures of social defeat stress response.

## Abstract

Stress-related psychiatric disorders impact the quality of life of half a billion people around the world. However, our understanding of the molecular mechanisms responsible for stress-response regulation remain unclear. Here, we report the largest and most comprehensive characterization of the adult male mouse hippocampus, under baseline and acute stress condition, using single-cell RNA sequencing. We further used genetically modified knockout lines for the glucocorticoid and mineralocorticoid receptors (GR and MR); two transcription factors which are pivotal regulators of the central stress-response. We found previously unknown, cell-type specific, molecular signatures of a single prolonged social defeat stress response and identified Nrgn and SgK1 as key regulators in stress-responsive glutamatergic neurons, oligodendrocytes, astrocytes, and endothelial cells. Intriguingly, GR or MR deletion, specifically in glutamatergic or GABAergic neurons, led to distinct and cell-type specific transcriptional signatures after stress exposure. This study significantly advances our understanding of the molecular and cellular network underlying the central response to stressful stimuli.