1. A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland
- Author
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Cai, Shang, Kalisky, Tomer, Sahoo, Debashis, Dalerba, Piero, Feng, Weiguo, Lin, Yuan, Qian, Dalong, Kong, Angela, Yu, Jeffrey, Wang, Flora, Chen, Elizabeth Y, Scheeren, Ferenc A, Kuo, Angera H, Sikandar, Shaheen S, Hisamori, Shigeo, van Weele, Linda J, Heiser, Diane, Sim, Sopheak, Lam, Jessica, Quake, Stephen, and Clarke, Michael F
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Stem Cell Research - Nonembryonic - Non-Human ,Regenerative Medicine ,Stem Cell Research ,Cancer ,Breast Cancer ,Animals ,Antigens ,CD ,Cell Cycle ,Cell Lineage ,Cell Proliferation ,Cyclin-Dependent Kinase Inhibitor p16 ,Cyclin-Dependent Kinase Inhibitor p21 ,Epithelial Cells ,Female ,Gene Deletion ,Homeostasis ,Mammary Glands ,Animal ,Mice ,Inbred C57BL ,Mice ,Knockout ,Regeneration ,Repressor Proteins ,Stem Cells ,Tumor Suppressor Proteins ,quiescence ,stem cell exhaustion ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Stem cells in many tissues sustain themselves by entering a quiescent state to avoid genomic insults and to prevent exhaustion caused by excessive proliferation. In the mammary gland, the identity and characteristics of quiescent epithelial stem cells are not clear. Here, we identify a quiescent mammary epithelial cell population expressing high levels of Bcl11b and located at the interface between luminal and basal cells. Bcl11bhigh cells are enriched for cells that can regenerate mammary glands in secondary transplants. Loss of Bcl11b leads to a Cdkn2a-dependent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. Gain- and loss-of-function studies show that Bcl11b induces cells to enter the G0 phase of the cell cycle and become quiescent. Taken together, these results suggest that Bcl11b acts as a central intrinsic regulator of mammary epithelial stem cell quiescence and exhaustion and is necessary for long-term maintenance of the mammary gland.
- Published
- 2017