Fused in sarcoma (FUS) inhibits milk production efficiency in mammals

Haili Shao, Jipeng Huang, Hui Wang, Guolei Wang, Xu Yang, Mei Cheng, Changjie Sun, Li Zou, Qin Yang, Dandan Zhang, Zhen Liu, Xuelong Jiang, Lei Shi, Peng Shi, Baowei Han () and Baowei Jiao ()
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Haili Shao: Chinese Academy of Sciences
Jipeng Huang: Chinese Academy of Sciences
Hui Wang: Chinese Academy of Sciences
Guolei Wang: Weifang People’s Hospital
Xu Yang: Chinese Academy of Sciences
Mei Cheng: Chinese Academy of Sciences
Changjie Sun: Chinese Academy of Sciences
Li Zou: Chinese Academy of Sciences
Qin Yang: Chinese Academy of Sciences
Dandan Zhang: Luoyang Maternal and Child Health Hospital
Zhen Liu: Chinese Academy of Sciences
Xuelong Jiang: Chinese Academy of Sciences
Lei Shi: Chinese Academy of Sciences
Peng Shi: Chinese Academy of Sciences
Baowei Han: Luoyang Maternal and Child Health Hospital
Baowei Jiao: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Efficient milk production in mammals confers evolutionary advantages by facilitating the transmission of energy from mother to offspring. However, the regulatory mechanism responsible for the gradual establishment of milk production efficiency in mammals, from marsupials to eutherians, remains elusive. Here, we find that mammary gland of the marsupial sugar glider contained milk components during adolescence, and that mammary gland development is less dynamically cyclic compared to that in placental mammals. Furthermore, fused in sarcoma (FUS) is found to be partially responsible for this establishment of low efficiency. In mouse model, FUS inhibit mammary epithelial cell differentiation through the cyclin-dependent kinase inhibitor p57Kip2, leading to lactation failure and pup starvation. Clinically, FUS levels are negatively correlated with milk production in lactating women. Overall, our results shed light on FUS as a negative regulator of milk production, providing a potential mechanism for the establishment of milk production from marsupial to eutherian mammals.

Date: 2024
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DOI: 10.1038/s41467-024-48428-5

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