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

被引：83

作者：

Cai, Shang ^{[1
]}

Kalisky, Tomer ^{[2
,7
]}

Sahoo, Debashis ^{[1
,3
]}

Dalerba, Piero ^{[1
,4
,5
]}

Feng, Weiguo ^{[1
,6
]}

Lin, Yuan ^{[1
,6
]}

Qian, Dalong ^{[1
]}

Kong, Angela ^{[1
]}

Yu, Jeffrey ^{[1
]}

Wang, Flora ^{[1
]}

Chen, Elizabeth Y. ^{[1
]}

Scheeren, Ferenc A. ^{[1
,8
]}

Kuo, Angera H. ^{[1
]}

Sikandar, Shaheen S. ^{[1
]}

Hisamori, Shigeo ^{[1
,9
]}

van Weele, Linda J. ^{[1
]}

Heiser, Diane ^{[1
]}

Sim, Sopheak ^{[1
]}

Lam, Jessica ^{[1
]}

Quake, Stephen ^{[2
]}

Clarke, Michael F. ^{[1
]}

机构：

[1] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA

[3] Univ Calif San Diego, Dept Comp Sci & Engn, Dept Pediat, San Diego, CA 92123 USA

[4] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[5] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[6] Stanford Univ, Sch Med, Inst Canc, Stanford, CA 94305 USA

[7] Bar Ilan Univ, Fac Engn, IL-52900 Ramat Gan, Israel

[8] Leiden Univ, Med Ctr, Dept Med Oncol, NL-2300 RC Leiden, Netherlands

[9] Kyoto Univ, Dept Surg, Sakyo Ku, 54 Kawaharacho, Kyoto 6068507, Japan

来源：

CELL STEM CELL | 2017年 / 20卷 / 02期

关键词：

DOWN-REGULATION; T-LYMPHOCYTES; SELF-RENEWAL; SENESCENCE; HETEROGENEITY; PROLIFERATION; GENE; P53; DIFFERENTIATION; IDENTIFICATION;

D O I：

10.1016/j.stem.2016.11.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 luminalandbasal 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 showthat Bcl11b induces cells to enter the G(0) phase of the cell cycle and become quiescent. Taken together, these results suggest that Bcl11b acts as a central intrinsic regulator of mammary epithelial stemcellquiescence and exhaustion and is necessary for long-term maintenance of the mammary gland.

引用

页码：247 / +

页数：19

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