Specification of the interstitial cell lineage in the fetal mouse ovary requires balanced Notch signaling

However, how these two lineages diverge during ovarian development remains unclear. By analyzing joint single-nucleus transcriptomic and chromatin accessibility profiles of murine ovarian cells at the onset of ovary formation, we identified two somatic progenitor populations from the coelomic epithelium distinguished by expression of the nuclear receptors Nr5a1 and Nr2f2.

Based on their transcriptomic trajectories, the Nr5a1+ epithelial cells preferentially transitioned toward the granulosa lineage whereas the Nr2f2+ epithelial cells differentiated into mesenchymal populations. This lineage relationship was supported by Nr2f2 lineage tracing experiments that fetal Nr2f2+ progenitors contribute to ovarian interstitial cells postnatally. To define the molecular features underlying this divergence, we performed differential gene expression and chromatin accessibility analyses and found that Nr2f2+ epithelial cells, but not Nr5a1+ cells, were enriched for Notch pathway components and Notch effector motifs.