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.
Bibliographical noteThis work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030000) and the CAS-Novonordisk Foundation, as well as grants from the ‘1000 talents’ recruitment program, and a ‘Great-wall professorship’ from the CAS-Novonordisk Foundation all to JRS. We are grateful to all the members of Molecular Energetics Group for their support and discussion of the results. We would like to thank the Center for Biological Imaging from Institute of Biophysics Chinese Academy of Sciences and Professor Zhaohui Wang's Lab from Institute of Genetics and Developmental Biology Chinese Academy of Sciences for confocal microscopy and the Center for Developmental Biology from Institute of Genetics and Developmental Biology Chinese Academy of Sciences and Dr. Jai from Core Facility for Protein Research from Institute of Biophysics Chinese Academy of Sciences for flow cytometry. We are grateful to Dr. Kuang from Purdue University and Dr. Zhu from Chinese Academy of Medical Sciences Peking Union Medical College for the kind donation of Myf5-Cre mice and Dr. Wolfrum from the Institute of Food Nutrition and Health at the ETH Zurich for the kind donation of the Ucp1-DTR mice. Xun Huang provided valuable comments on previous versions of the manuscript.
- Journal Article
- Brown adipocytes
- Mammary gland
- Basal myoepithelial cells
- Beige/brite adipocytes