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A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland.
- Source :
-
Cell stem cell [Cell Stem Cell] 2017 Feb 02; Vol. 20 (2), pp. 247-260.e5. Date of Electronic Publication: 2016 Dec 29. - Publication Year :
- 2017
-
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. Bcl11b <superscript>high</superscript> 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 G <subscript>0</subscript> 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antigens, CD metabolism
Cell Lineage
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p16 metabolism
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Epithelial Cells metabolism
Female
Gene Deletion
Homeostasis
Mammary Glands, Animal growth & development
Mice, Inbred C57BL
Mice, Knockout
Regeneration physiology
Cell Cycle
Mammary Glands, Animal cytology
Mammary Glands, Animal metabolism
Repressor Proteins metabolism
Stem Cells cytology
Stem Cells metabolism
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1875-9777
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell stem cell
- Publication Type :
- Academic Journal
- Accession number :
- 28041896
- Full Text :
- https://doi.org/10.1016/j.stem.2016.11.007