Dormant Nfatc1 reporter-marked basal stem/progenitor cells contribute to mammary lobuloalveoli formation

Ruiqi Liu; Huan Hu; Melissa McNeil; Jiuzhi Xu; Xueyun Bi; Pengbo Lou; Christian F Guerrero-Juarez; Xing Dai; Maksim V Plikus; Jianwei Shuai; Zhengquan Yu; Cong Lv

doi:10.1016/j.isci.2022.103982

Dormant Nfatc1 reporter-marked basal stem/progenitor cells contribute to mammary lobuloalveoli formation

iScience. 2022 Feb 26;25(3):103982. doi: 10.1016/j.isci.2022.103982. eCollection 2022 Mar 18.

Authors

Ruiqi Liu¹, Huan Hu², Melissa McNeil³, Jiuzhi Xu¹, Xueyun Bi¹, Pengbo Lou¹, Christian F Guerrero-Juarez⁴, Xing Dai³, Maksim V Plikus⁴, Jianwei Shuai^{2

5}, Zhengquan Yu¹, Cong Lv⁶

Affiliations

¹ State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
² Department of Physics, and National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen 361005, China.
³ Departments of Biological Chemistry and Dermatology, School of Medicine, Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA.
⁴ 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.
⁵ Wenzhou Institute, University of Chinese Academy of Sciences, and Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China.
⁶ Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.

Abstract

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.

Keywords: Biological sciences; Molecular physiology; Omics; Stem cells research.

Abstract

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