A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland

Publication date: Available online 29 December 2016
Source:Cell Stem Cell
Author(s): Shang Cai, Tomer Kalisky, Debashis Sahoo, Piero Dalerba, Weiguo Feng, Yuan Lin, Dalong Qian, Angela Kong, Jeffrey Yu, Flora Wang, Elizabeth Y. Chen, Ferenc A. Scheeren, Angera H. Kuo, Shaheen S. Sikandar, Shigeo Hisamori, Linda J. van Weele, Diane Heiser, Sopheak Sim, Jessica Lam, Stephen Quake, Michael F. Clarke
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. Bcl11b^high 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.

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Teaser

Bcl11b interacts with cell-cycle regulators to induce a quiescent state. Cai et al. describe a quiescent mammary stem cell population labeled by Bcl11b and located at the luminal-basal interface that supports mammary gland regeneration. Bcl11b sustains this population by inducing cell-cycle regulators that promote the dormant state.


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