A spatiotemporal gene expression and cell atlases of the developing rat ovary.

Normal ovarian development is necessary for the production of healthy oocytes. However, the characteristics of oocytes development at different stages and the regulatory relationship between oocytes and somatic cells remain to be fully explained. Here, we combined scRNA-seq and spatial transcriptomic sequencing to profile the transcriptomic atlas of developing ovarian of the rat. We identified four components from developing granulosa cells including cumulus, primitive, mural, and luteal cells, and constructed their differential transcriptional regulatory networks. Several novel growth signals from oocytes to cumulus cells were identified, such as JAG1-NOTCH2 and FGF9-FGFR2. Moreover, we observed three cumulus sequential phases during follicle development determined by the key transcriptional factors in each cumulus phase (Bckaf1, Gata6, Cebpb, etc.), as well as the potential pinpointed roles of macrophages in luteal regression. Altogether, the single-cell spatial transcriptomic profile of the ovary provides not only a new research dimension for temporal and spatial analysis of ovary development, but also valuable data resources and a research basis for in-depth excavation of the mechanisms of mammalian ovary development.