EHF is an essential driver of mammary alveolar lineage differentiation and putative suppressor of breast tumorigenesis

The Ets homologous factor (Ehf) is highly expressed in the mammary gland in pregnancy and lactation. Mothers with Ehf deletion fail to lactate due to impaired lobuloalveolar development. scRNA-seq profiling of mammary epithelial cells (MECs) at late pregnancy (18.5dP) demonstrated that EhfKO mammary gland comprised fewer differentiated alveolar cells, and an accumulation of the preceding cell populations in the secretory differentiation hierarchy. EhfKO mammary alveolar cells also displayed significant downregulation of milk proteins and lipids, and increased expression of proliferation markers indicating incomplete differentiation Single cell RNA sequencing of mammary epithelial cells (Ter119–CD31−CD45–) from mice with and without deletion of Ehf at late pregnancy (18.5 days pregnant)

ETS同源因子（Ets homologous factor, Ehf）在妊娠及泌乳期的乳腺中呈高表达。携带Ehf缺失的母鼠无法泌乳，其原因是腺泡小叶发育受损。对妊娠晚期（18.5dP）的乳腺上皮细胞（mammary epithelial cells, MECs）开展单细胞RNA测序（single cell RNA sequencing, scRNA-seq）分析发现，Ehf敲除（Ehf knockout, EhfKO）的乳腺中，分化成熟的腺泡细胞数量更少，且分泌分化层级中的前置细胞群出现异常累积。此外，Ehf敲除的乳腺腺泡细胞还表现出乳蛋白与脂类的显著下调，同时增殖标志物的表达水平升高，提示细胞分化不完全。本数据集的测序样本来自妊娠晚期（妊娠18.5天）Ehf缺失与未缺失小鼠的乳腺上皮细胞（Ter119–CD31−CD45–）。