Single-cell transcriptomic atlas of mouse oocyte development from growth to ovulation

Abstract Oocyte growth and maturation depend on tightly coordinated programs within oocytes and their surrounding granulosa cells, yet defining the transcriptional continuum of growing oocytes has been challenging due to their large size and the limitations of current droplet-based and spatial transcriptomic platforms. Here, we optimized a high-density array–based platform called Stereo-cell for high-throughput dual-modality profiling of large mouse oocytes, allowing for both the preservation of morphology and transcript capture. By integrating unsupervised transcriptomic clustering with cell morphological features, we delineated successive temporal windows from growing oocytes to metaphase II and uncovered stage-linked shifts from early programs toward later programs. We also profiled the ovarian somatic fraction, reconstructed granulosa-cell subtype relationships, and placed ovarian cell states in tissue context using single-cell–resolution spatial data.