8574 Single-Cell Assessment of Gene Expression of the Tuberal Hypothalamus and Preoptic Area From Birth to Puberty in Male and Female Mice

Abstract Disclosure: D. Ruiz: None. V. Corces: None. The hypothalamus houses numerous cell types that control essential physiological functions and behaviors. Early postnatal life is a critical period of development where hypothalamic cells mature in function, hypothalamic circuits are refined, and sex differences in cell populations are established. Nonetheless, we have a limited understanding of the cell-specific changes in gene expression that occur throughout hypothalamic postnatal development. Having a detailed understanding of transcriptomic dynamics during this critical period of development will help our understanding of metabolic, reproductive, and behavioral disorders whose pathogenesis has been linked to insults during early postnatal life. Here, we perform single-cell RNA seq separately in microdissected tuberal hypothalamus and preoptic area (POA) from C57Bl6/J male and female mice at multiple time points throughout postnatal development, including within an hour after birth, during minipuberty and puberty. We identify changes in gene expression in cells that control reproduction including GnRH and GnIH neurons, as well as Kisspeptin neurons from the Arcuate nucleus and the Anteroventral Periventricular nucleus. We also identify changes in cell types that control appetite, including POMC and AgRP neurons, as well as SF-1 neurons of the Ventromedial Hypothalamus. Subclustering of neurons allows us to identify extensive transcriptomic heterogeneity in some well-known hypothalamic neurons that can help us understand previously unrecognized functions. Additionally, we find extensive transcriptomic changes in non-neuronal cells, including microglia, astrocytes, ependymal cells, and cells from the pars tuberalis throughout postnatal development. Current work aims to understand the function and physiological relevance of these extensive temporal and sex-driven changes in gene expression. Presentation: 6/2/2024