S100A4+ stromal cells are required for functional nipple development and successful nursing

Depleting S100A4+ stromal cells in S100a4-Cre;DTA dams causes a severe nursing defect with complete litter loss within the first day postpartum.

• Why it matters: Nipple and mammary development rely on mesenchymal signals, but the specific identity and functional contribution of S100A4+ cells during lactation were unclear.
• What they did: Using S100a4-Cre;DTA cell depletion, the study assessed lactation outcomes, then combined immunofluorescence, oxytocin stimulation assays, lineage tracing, and bulk RNA sequencing of nipple tissue.
• The result: Mammary morphology, milk production, and alveolar contractility were normal, yet nipple development was defective and nipple tissue showed inflammatory signatures, implicating S100A4+ fibroblasts and immune cells in successful lactation.

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