Depletion of S100A4+ Stromal Cells Results in Abnormal Nipple Development and Nursing Failure

The study investigates the role of S100A4-positive (S100A4+) stromal cells in nipple and mammary development using a mouse model. Depletion of these cells in S100a4-Cre;DTA mice resulted in severe nursing defects and complete litter loss within the first day postpartum, despite normal mammary morphology, milk production, and alveolar contractility. The research identified defective nipple development and inflammatory signatures in nipple tissue. S100A4+ cells were found to be fibroblasts and immune cells in the nipple, while only immune cells expressed S100A4 in the mammary gland. This study reveals the critical role of S100A4+ cells in nipple development, emphasizing their importance for successful lactation and providing insights for breastfeeding medicine.