Olfactomedin 4 marks progenitor cells that give rise to the secretory cell lineage in the mouse cervix

Goblet cells, a specialized secretory cell type of mucosal epithelia, provide barrier function to the female lower reproductive tract. Current understanding proposes that squamous and secretory cells of the mouse cervicovaginal epithelium arise from a common Trp63+ progenitor. By contrast, in humans, a Krt8+ progenitor gives rise to endocervical secretory cells, whereas a Trp63+ progenitor gives rise to squamous cells in the ectocervix and vagina. We identify a population of Krt8+Trp63- epithelia that is retained in the mouse cervicovaginal epithelium during postnatal development and adulthood, with Olfactomedin 4 as a specific marker of this lineage. Adult lineage tracing and marker assessment during postnatal development support a revised model in which two epithelial progenitors are delineated by postnatal day 15. Olfactomedin4+ progenitors give rise to goblet cells, while Trp63+ progenitors give rise to keratinocytes in the cervicovaginal canal. Consistent with goblet cell expansion in pregnancy, Olfm4+ progenitors proliferate in early gestation and progesterone promotes their differentiation. These findings reveal a previously unrecognized similarity between mice and humans in which goblet and keratinized cell subtypes are derived from two independent progenitor populations.