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Cell Stem Cell. 2017 Feb 2;20(2):247-260.e5. doi: 10.1016/j.stem.2016.11.007. Epub 2016 Dec 29.

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

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA.
2
Department of Bioengineering, School of Medicine, Stanford University, Stanford, CA 94305, USA.
3
Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Department of Computer Science and Engineering, University of California San Diego, San Diego, CA 92123-0984, USA.
4
Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
5
Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA; Cancer Institute, School of Medicine, Stanford University, Stanford, CA 94305, USA.
6
Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: mfclarke@stanford.edu.

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.

KEYWORDS:

quiescence; stem cell exhaustion

PMID:
28041896
PMCID:
PMC5341693
DOI:
10.1016/j.stem.2016.11.007
[Indexed for MEDLINE]
Free PMC Article

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