A functional cellular framework for sex and estrous cycle-dependent gene expression and behavior

性别和发情周期依赖性基因表达和行为的功能细胞框架

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作者:Joseph R Knoedler, Sayaka Inoue, Daniel W Bayless, Taehong Yang, Adarsh Tantry, Chung-Ha Davis, Nicole Y Leung, Srinivas Parthasarathy, Grace Wang, Maricruz Alvarado, Abbas H Rizvi, Lief E Fenno, Charu Ramakrishnan, Karl Deisseroth, Nirao M Shah

Abstract

Sex hormones exert a profound influence on gendered behaviors. How individual sex hormone-responsive neuronal populations regulate diverse sex-typical behaviors is unclear. We performed orthogonal, genetically targeted sequencing of four estrogen receptor 1-expressing (Esr1+) populations and identified 1,415 genes expressed differentially between sexes or estrous states. Unique subsets of these genes were distributed across all 137 transcriptomically defined Esr1+ cell types, including estrous stage-specific ones, that comprise the four populations. We used differentially expressed genes labeling single Esr1+ cell types as entry points to functionally characterize two such cell types, BNSTprTac1/Esr1 and VMHvlCckar/Esr1. We observed that these two cell types, but not the other Esr1+ cell types in these populations, are essential for sex recognition in males and mating in females, respectively. Furthermore, VMHvlCckar/Esr1 cell type projections are distinct from those of other VMHvlEsr1 cell types. Together, projection and functional specialization of dimorphic cell types enables sex hormone-responsive populations to regulate diverse social behaviors.

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