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

Why It Matters

The dataset uncovers cell‑type‑specific molecular signatures of acute stress, providing new therapeutic targets and a benchmark for future psychiatric disorder studies.

Key Takeaways

• 125,896 hippocampal cells profiled across genotypes and stress.
• Nrgn marks stress‑responsive glutamatergic neuron subpopulations.
• Sgk1 sharply induced in mature oligodendrocytes after stress.
• GR/MR deletions cause heterogeneous neuronal transcriptional signatures.
• Dataset released on CELLxGENE for community use.

Pulse Analysis

Single‑cell RNA‑sequencing has become indispensable for dissecting brain complexity, yet comprehensive atlases of stress‑responsive regions remain scarce. By sequencing nearly 130,000 hippocampal cells from adult male mice, the study delivers an unprecedented resolution of neuronal, glial, and vascular populations under both baseline and acute social defeat conditions. The rigorous experimental design—incorporating wild‑type, GR‑conditional, and MR‑conditional knockouts—paired with advanced batch correction and trajectory inference, ensures that observed transcriptional shifts reflect genuine biological responses rather than technical artifacts.

Among the most compelling discoveries are two cell‑type‑specific stress markers. Neurogranin (Nrgn) emerged as a consistent identifier of stress‑reactive glutamatergic neurons across CA1, CA3, and dentate gyrus subfields, linking synaptic plasticity pathways to acute stress exposure. In parallel, serum‑ and glucocorticoid‑regulated kinase 1 (Sgk1) showed a nine‑fold increase in mature oligodendrocytes, highlighting an underappreciated glial contribution to the hypothalamic‑pituitary‑adrenal axis. Conditional deletion of GR or MR produced divergent neuronal transcriptional signatures, underscoring the nuanced interplay between receptor signaling and cell identity, while non‑neuronal cells responded more uniformly.

The public release of this dataset on CELLxGENE equips researchers with a searchable, downloadable resource to validate hypotheses, perform cross‑species comparisons, and accelerate drug target discovery. Although limited to male mice and the posterior hippocampus, the work sets a methodological benchmark for future investigations into sex differences, ventral hippocampal dynamics, and chronic stress models. By mapping stress‑induced molecular landscapes at single‑cell resolution, the study paves the way for precision‑medicine approaches to psychiatric disorders.