Reproductive seasonality serves as a critical life-history strategy, that significantly influences the fitness of organisms in nature. While some species adapt to seasonal cues such as photoperiods, others change or even lose their seasonality. Understanding the evolutionary mechanisms of reproductive seasonality is crucial for predicting the ecological impacts of climate change and assessing extinction risks for biodiversity conservation. Despite its importance, the molecular genetic mechanisms that facilitate the diversification of reproductive seasonality remain largely unexplored. To address this gap, we used the three-spined stickleback, a model organism known for its diverse photoperiodic responses in reproduction across different ecotypes. Using RNAseq and functional analyses, we found that thyroid-stimulating hormone-β2 (TSHβ2) dynamically modulates its expression in response to day length, thereby controlling a range of downstream physiological and behavioral traits. Moreover, the pituitary gland, which is responsible for TSHβ2 production, exhibits substantial heterogeneity in both transcriptional regulations and epigenetic modifications. To delve deeper into the TSHβ2 regulatory network, we performed single-cell transcriptomic and epigenetic profiling of the pituitary gland. Our results revealed a novel cell type that uniquely produces TSHβ2. Furthermore, these TSHβ2 producing cells showed increased chromatin accessibility in the region approximately 3kb upstream of the TSHβ2 gene under short-day conditions, suggesting transcriptional and epigenetic modifications in response to photoperiodic changes. Overall, our work highlights the pivotal role of TSHβ2-producing cells in the evolutionary adaptation of reproductive seasonality. These findings suggest that the TSHβ2-producing cell functions as a pleiotropic hub, coordinating the onset of various reproductive activities.
TSHβ2-producing cell: A key orchestrator of reproductive seasonality in sticklebacks