Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species

Abstract

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 TRPC4 as a conserved molecular marker of the mouse and human LS, while FREM2 is enriched only in the human LS. We also identify a distinct neuronal cell type marked by OPRM1 , the gene encoding the μ-opioid receptor. Together, these results highlight transcriptional heterogeneity of the human LS and identify robust marker genes for the human LS.