Cell-type-specific architecture of the hypothalamus in a socially plastic vertebrate
Dussenne, M.; Castillo, M.; Gunaratne, P.; Hoadley, A. P.; Saenz, L. A.; Alward, B. A.
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The hypothalamus orchestrates social behaviors by integrating physiological state with environmental information, but the cellular substrates of this plasticity remain unresolved. We combined single-cell and spatial transcriptomics to generate a cell-type map of the hypothalamus in Astatotilapia burtoni, a cichlid fish that forms dynamic social hierarchies. We identified 28 neuronal, glial, neurogenic, and immune cell populations and mapped their organization across hypothalamic nuclei. Social status, sex, and reproductive state engaged coordinated, cell-type-specific transcriptional programs, revealing modular deployment of steroid hormone signaling and plasticity-associated genes. The atlas identified elevated sst1.1 expression in the hypothalamus of dominant males that we localized to the teleost VMH. CRISPR-Cas9 disruption of sst1.1 increased body size, suggesting a role for optimal metabolic and energy allocation. These results define a cellular framework for understanding how hypothalamic plasticity enables flexible social behavior.
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