The estrous cycle transcriptional and chromatin dynamics in pituitary cell types have not been investigated. We report single-nucleus multiomics assays in 18 adult mouse pituitaries (102,069 post quality-control nuclei) across 6 cycle time points. Differential analysis revealed cycle stage-dependent epigenetic and transcriptional remodeling across the major pituitary cell populations. In gonadotropes and lactotropes, we identified temporal patterns of differential gene expression linked to various biological processes, notably neuronal and synaptic-related ontologies. Pseudotime trajectory analysis was consistent with a rapid transition of individual gonadotropes through different cellular states. In gonadotropes and lactotropes, we uncovered gene regulatory circuits whose activity varies between consecutive cycle time points. We experimentally validated a gonadotrope ETS2-driven circuit that differentially regulates Fshb gene expression between 2 and 9 am on estrus. Our data and analyses, available at https://rstudio-connect.hpc.mssm.edu/snpit_estrous_browser/, provide a window into gene regulatory mechanisms underlying estrous cycle stage transitions.
Zhang, Z., Cheng, W. S., Jin, Y., Ongaro, L., Smith, G. R., Pincas, H., Mendelev, N., Strupinsky, G., Alonso, C. A. I., Zhou, X., Brule, E., Zamojski, M., Turgeon, J. L., Zaslavsky, E., Bernard, D. J., Ruf-Zamojski, F., Sealfon, S.
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