Brown adipocytes can display a mammary basal myoepithelial cell phenotype in vivo

Abstract

Objective: Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. Methods: To investigate the putative adipocyte origin of mammary gland cells, we performed genetic lineage-labeling experiments in BAT and the mammary glands. Results: These studies indicated that the classic brown adipocytes (Ucp1+) and subcutaneous beige/brite adipocytes (Ucp1−/+) were found in the mammary gland during lactation, when they exhibited a mammary myoepithelial phenotype. Up to 2.5% of the anterior dorsal interscapular mammary myoepithelial cell population had a brown adipocyte origin with an adipose and myoepithelial gene signature during lactation. Eliminating these cells, along with all the brown adipocytes, significantly slowed offspring growth, potentially demonstrating their functional importance. Additionally, we showed mammary epithelial lineage Mmtv+ and Krt14+ cells expressed brown adipocyte markers after weaning, demonstrating that mammary gland cells can display an adipose phenotype. Conclusions: The identification of a brown adipocyte origin of mammary myoepithelial cells provides a novel perspective on the interrelationships between adipocytes and mammary cells with implications for our understanding of obesity and breast cancer.

Keywords

• Brown adipocytes
• Mammary gland
• Lactation
• Basal myoepithelial cells
• Beige/brite adipocytes