The Ets transcription factor Elf5 specifies mammary alveolar cell fate

TLDR

Hormonal signals drive mammary development, yet the transcriptional changes and cell fate decisions they trigger remain largely unknown. Elf5 is essential for alveolar lineage specification: its loss blocks secretory epithelium formation and causes CD61⁺ progenitor accumulation, while its ectopic expression drives alveolar differentiation and milk secretion in virgin mice, linking prolactin signaling to alveolar development.

Abstract

Hormonal cues regulate mammary development, but the consequent transcriptional changes and cell fate decisions are largely undefined. We show that knockout of the prolactin-regulated Ets transcription factor Elf5 prevented formation of the secretory epithelium during pregnancy. Conversely, overexpression of Elf5 in an inducible transgenic model caused alveolar differentiation and milk secretion in virgin mice, disrupting ductal morphogenesis. CD61 + luminal progenitor cells accumulated in Elf5-deficient mammary glands and were diminished in glands with Elf5 overexpression. Thus Elf5 specifies the differentiation of CD61 + progenitors to establish the secretory alveolar lineage during pregnancy, providing a link between prolactin, transcriptional events, and alveolar development.