Escort-like somatic cells mediate early mouse fetal ovarian development but surface-derived Lgr5+ cells support primordial follicles

Abstract

AbstractOvarian murine somatic cells are essential to form first wave medullar follicles and second wave primordial follicles. Using single cell RNA sequencing we characterized the transcriptomes of both somatic and germline ovarian cells during fetal and early neonatal development. Wnt4-expressing somatic cells we term “escort-like cells (ELCs)” interact with incoming germ cells and early developing cysts of both sexes. In the medullar region, ELCs differentiate into the granulosa cells of fast-growing first wave follicles. In contrast, after E12.5, Lgr5+ pre-granulosa cells ingress from the ovarian surface epithelium and replace cortical escort-like cells. These surface-derived cells become the main population of granulosa cells supporting primordial follicles, and differ in transcription from ELC derivatives. Reflecting their different cellular origins, ablation of Lgr5+ cells at E16.5 using Lgr5-DTR-EGFP eliminates second wave follicles, but first wave follicles continue to develop normally and support fertility. Our findings provide striking evidence that somatic cell behavior supporting germline cyst development in mice and Drosophila has been evolutionarily conserved.