biostudies-literatureUnknown28(2)Phillips RANational Institute of Mental HealthLieber Institute for Brain DevelopmentThe lateral septum (LS) is a midline, subcortical structure that is a critical regulator of social behaviors. Mouse studies have identified molecularly distinct neuronal populations within the LS, which control specific facets of social behavior. Despite its known molecular heterogeneity in the mouse and critical role in regulating social behavior, comprehensive molecular profiling of the human LS has not been performed. Here, we conducted single-nucleus RNA sequencing (snRNA-seq) to generate transcriptomic profiles of the human LS and compared human LS profiles to recently collected mouse LS snRNA-seq datasets. Our analyses identified <i>TRPC4</i> as a conserved molecular marker of the mouse and human LS, while <i>FREM2</i> is enriched only in the human LS. We also identify a distinct neuiScience111820https://www.ebi.ac.uk/biostudies/studies/S-EPMC11834073biostudies-literatureTranscriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species.PMC11834073Martinowich KPage SCKleinman JEMiller RAOh SDu YBach SVHyde TMHicks SCPhillips RAfalseTranscriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species.The lateral septum (LS) is a midline, subcortical structure that is a critical regulator of social behaviors. Mouse studies have identified molecularly distinct neuronal populations within the LS, which control specific facets of social behavior. Despite its known molecular heterogeneity in the mouse and critical role in regulating social behavior, comprehensive molecular profiling of the human LS has not been performed. Here, we conducted single-nucleus RNA sequencing (snRNA-seq) to generate transcriptomic profiles of the human LS and compared human LS profiles to recently collected mouse LS snRNA-seq datasets. Our analyses identified <i>TRPC4</i> as a conserved molecular marker of the mouse and human LS, while <i>FREM2</i> is enriched only in the human LS. We also identify a distinct neu2025-01-01T00:00:00Z2025 Feb2026-06-02T04:10:01.187Z2025-04-19T21:15:22.823ZS-EPMC118340733996786310.1016/j.isci.2025.111820