Divergent aging of nulliparous and parous mammary glands reveals IL33+ hybrid epithelial cells.

ABSTRACT: Aging increases breast cancer risk while an early first pregnancy reduces a woman's life-long risk. Several studies have explored the effect of either aging or pregnancy on mammary stem/progenitor cells, however, the combined effect of both remains unclear. Here, we interrogate the functional and transcriptomic changes at single-cell resolution in the mammary gland of aged nulliparous and parous mice to discover that pregnancy normalizes age-related imbalances in lineage composition, while also inducing a differentiated cell state. Importantly, we uncover a minority population of Il33-expressing epithelial cells that express both luminal and basal markers (i.e. hybrid), which accumulate in aged nulliparous mice but are significantly reduced in aged parous mice. Functionally, IL33 treatment

SUBMITTER: Olander A 

PROVIDER: S-EPMC12923676 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature