Single-nucleus RNA sequencing reveals cellular heterogeneity in the lateral septal area of mice with different immune backgrounds

We employed single-nucleus RNA sequencing (snRNA-seq) using the 10x Genomics platform to investigate the cellular heterogeneity and gene expression changes in the lateral septum (LS) region of mice with different immune backgrounds. The LS serves as a central hub for regulating emotional responses in the brain and may be influenced by the host's immune status. Notably, C57J, BALB/c, and nude mice exhibit distinct behavioral differences in open field and fear memory tests. To further explore the underlying molecular mechanisms, we performed snRNA-seq analysis on the LS region of these three mouse strains, aiming to elucidate how immune background shapes the cellular architecture and transcriptional landscape of the LS. Overall design: The lateral septum (LS) regions were microdissected from C57J, BALB/c, and nude mice under a stereomicroscope and immediately snap-frozen at -80 °C for preservation. Prior to sequencing, the frozen tissues were thawed and processed for single-nucleus isolation, followed by single-nucleus RNA sequencing (snRNA-seq) analysis.