Transcriptome Dynamics and Cell Dialogs Between Oocytes and Granulosa Cells in Mouse Follicle Development

Abstract The development and maturation of follicles is a sophisticated and multistage process. The dynamic gene expression of oocytes and the surrounding somatic cells and the dialogs between these cells are critical to this process. We accurately classified the follicle development into nine stages and profiled the gene expression of mouse oocytes, the companion granulosa cells, and cumulus cells. The clustering of the transcriptomes showed the trajectory to the two distinct development courses of oocytes and the surrounding somatic cells. Gene expression changes precipitously increased at Type 4 stage and drastically droped afterwards within both oocytes and granulosa cells. Moreover, the number of differentially expressed genes between oocytes and granulosa cells dramatically increased at Type 4 stage, most of which persistently passed on to the later stages. Strikingly, cell communications within and between oocytes and granulosa cells became active from Type 4 onwards. Cell dialogs connected oocytes and granulosa cells in both unidirectional and bidirectional manners. TGFB2/3, TGFBR2/3, INHBA/B, and ACVR1/1B/2B of TGF-β signaling pathway functioned in the follicle development. NOTCH signaling pathway regulated the development of granulosa cells. Additionally, many maternally DNA methylation- or H3K27me3-imprinted genes remained active in granulosa cells but silent in oocytes during oogenesis. Collectively, Type 4 is the key turning point when significant transcription changes diverge the fate of oocytes and granulosa cells, and the cell dialogs become active to assure follicle development. These findings shed new insights into transcriptomic dynamics and cell dialogs facilitating the development and maturation of oocytes and follicles.