State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
Huan Hu
Department of Physics, and National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen 361005, China
Melissa McNeil
Departments of Biological Chemistry and Dermatology, School of Medicine, Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA
Jiuzhi Xu
State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
Xueyun Bi
State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
Pengbo Lou
State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
Christian F. Guerrero-Juarez
Department of Developmental and Cell Biology, NSF-Simons Center for Multiscale Cell Fate Research, Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA
Xing Dai
Departments of Biological Chemistry and Dermatology, School of Medicine, Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA
Maksim V. Plikus
Department of Developmental and Cell Biology, NSF-Simons Center for Multiscale Cell Fate Research, Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA
Jianwei Shuai
Department of Physics, and National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen 361005, China; Wenzhou Institute, University of Chinese Academy of Sciences, and Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China; Corresponding author
Zhengquan Yu
State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Corresponding author
Cong Lv
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; Corresponding author
Summary: The Mammary gland undergoes complicated epithelial remodeling to form lobuloalveoli during pregnancy, in which basal epithelial cells remarkably increase to form a basket-like architecture. However, it remains largely unknown how dormant mammary basal stem/progenitor cells involve in lobuloalveolar development. Here, we show that Nfatc1 expression marks a rare population of mammary epithelial cells with the majority being basal epithelial cells. Nfatc1 reporter-marked basal epithelial cells are relatively dormant mammary stem/progenitor cells. Although Nfatc1 reporter-marked basal epithelial cells have limited contribution to the homeostasis of mammary epithelium, they divide rapidly during pregnancy and contribute to lobuloalveolar development. Furthermore, Nfatc1 reporter-marked basal epithelial cells are preferentially used for multiple pregnancies. Using single-cell RNA-seq analysis, we identify multiple functionally distinct clusters within the Nfatc1 reporter-marked cell-derived progeny cells during pregnancy. Taken together, our findings underscore Nfatc1 reporter-marked basal cells as dormant stem/progenitor cells that contribute to mammary lobuloalveolar development during pregnancy.
