Single-cell transcriptomics reveals extracellular matrix remodeling and collagen dynamics during lactation in sheep...

The mammary gland is a dynamic organ with diverse cell populations that maintain glandular homeostasis, particularly during lactation. However, the cellular architecture and molecular mechanisms underlying lactational remodeling in the sheep mammary gland remain incompletely understood. Given similarities in mammary stromal structure, sheep serve as a valuable model for studying lactational changes relevant to the human breast, which experiences collagen loss and sagging during lactation. Utilizing single-cell transcriptomics (scRNA-seq), we mapped the sheep mammary gland's cellular landscape at postpartum days 60 and 150, identifying seven major cell types, including six distinct epithelial clusters. These clusters revealed differentiation among luminal progenitors, hormone-sensing, and myoepithelial cells across peak and late lactation stages. Transcriptomic analysis highlighted pivotal roles for epithelial integrity and ECM remodeling, with myoepithelial cells centrally involved in these processes. We observed significant collagen remodeling driven by fibroblast-epithelial crosstalk and ECM reorganization during late lactation. Comparative analysis with human mammary epithelial cells showed conserved basal and myoepithelial cell populations, while luminal cells diverged across species. This study provides insights into lactation biology and ECM remodeling, offering a framework to inform future studies on lactational adaptation and its implications for human health.